huFcγRII线性结合表位的鉴定及对SLE小鼠的治疗效果
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摘要
为获得huFcγRII胞外区蛋白,将huFcγRII胞外区cDNA亚克隆到原核表达载体pET-28a,结果在大肠杆菌中高效表达了huFcγRII胞外区,以快速稀释复性方法从包涵体变性蛋白中回收了具有良好结合活性的huFcγRII重组蛋白。为研究huFcγRII的功能,将huFcγRII编码区cDNA亚克隆到真核表达载体pcDNA3,转染COS-7细胞,在细胞表面表达该受体分子,通过G418抗性筛选和连续克隆化,结果获得了稳定表达huFcγRII的转染细胞株。
为鉴定huFcγRII的线性结合表位,在EC2结构域设计合成huFcγRII多肽,偶联于载体蛋白BSA;以Dot-blot检测偶联多肽与人IgG的结合,并对阳性多肽进行进一步缺失分析。Dot-blot分析表明huFcγRII的151-163位多肽CTGNIGYTLFSSK是特异结合人IgG的有效多肽,为huFcγRII的线性结合表位,位于受体EC2结构域F-G环。含有huFcγRII线性结合表位的多肽不仅有效抑制人IgG与可溶性huFcγRII的结合,而且对huFcγRII转染细胞表面的IgG-FITC免疫荧光强度也具有良好的抑制功效,表明该结合表位多肽具有调节人IgG与细胞表面huFcγRII结合的能力,是首次发现的人FcR上存在线性结合表位。
为验证huFcγRII线性结合表位在体内的功能,将该多肽进行了动物实验。SLE小鼠模型实验表明该表位多肽提高了小鼠存活率,降低了严重蛋白尿比例和肾脏损伤程度,说明huFcγRII多肽对SLE模型小鼠的病情具有一定的延缓作用,对开发治疗自身免疫疾病的FcR靶标药物提供了参考。
Fc receptors are a group of important molecules expressed on the surface of immune accessory and effector cells, which bind the Fc region of immunoglobulins with specific affinities and have a number of important biological functions. FcRs play a crucial role in immune regulation by providing a link between the humoral and cellular responses. The antibody-mediated inflammatory response is regulated by activating and inhibitory FcRs. Thus, FcR-targeting provides therapies for allergy and autoimmune diseases. In this study using synthetic peptides we identified and characterized a linear epitope sequence in huFcγRII involved in the binding of human IgG. This is the first report describing linear epitopes on human FcRs capable of Fc-binding. This should further our understanding of the molecular mechanism of the FcγR-IgG interaction, and may provide a basis for the design of drugs with a potential for regulating antibody-mediated inflammation.
HuFcγRII is a low-affinity Fc receptor with two extracellular Ig-like domains and binds human IgG via the membrane proximal extracellular domain 2(EC2). To obtain a protein product equivalent to the extracellular domain of the huFcγRII, this domain of the huFcγRII gene was amplified from the recombinant plasmid ThuRII by PCR and then cloned into the pET-28a vector. The recombinant plasmid pETshuRII, after identification by PCR and double digestion, was transformed into E.coli BL21 (DE3). The results of SDS-PAGE showed that the molecular mass (M r) of the expressed protein was 24.8×103, and the expression rate was 30%.The washed inclusion bodies contained recombinant shuRII at up to 90% purity. The recombinant protein was dissolved in 6 M guanidine buffer, and then refolded by rapid dilution. ELISA showed that the refolded shuRII was able to bind human IgG in a dose dependent manner and using flow cytometry, that it competitively inhibited the binding of human IgG to huFcγRII expressed on the surface of COS-7 cells. These results demonstrate that it is possible to obtain large quantities of recombinant shuRII with comparable IgG binding properties to that of the whole membrane bound huFcγRII.
In order to express the receptor at the surface of a cultured cell, huFcγRII cDNA was cloned from human peripheral blood leucocytes by RT-PCR and a huFcγRII-expressing plasmid (pcDNA3-huFcγRII) was constructed. After verification by restriction digestion and PCR, the recombinant plasmid was transfected into COS-7 cells using lipofectamine. After screening by G418, a stable cell line expressing the receptor, identified by immunofluorescence and rosetting assays, was established. The result confirmed that the eukaryotic expression plasmid pcDNA3-huFcγRII was successfully constructed, and that the gene was transfected stably into COS-7 cells providing a solid experimental foundation for further investigation on the function of the huFcγRII gene.
To identify the linear epitope for Fc-binding on huFcγRII, peptides derived from the EC2 domain of huFcγRII were synthesized and coupled to BSA as carrier protein. Binding of human IgG to the different peptides was tested by Dot-blot assay. The effective peptide corresponding to the sequence 151-163 of huFcγRII located in the putative F-G loop of the EC2 domain possessed the ability to bind human IgG. The coupled peptide containing the IgG-binding epitope efficiently inhibited the binding of human IgG to soluble huFcγRII as well as to transfected COS-7 cells expressing huFcγRII. The Fc-binding epitope peptide showed the capability of modulating the interaction of IgG and huFcγRII on cell surface.
To study potential therapeutic properties of the peptide RII6-C6 in immune complex-mediated autoimmune disease, Female MRL/lpr mice (six weeks old) were purchased from SLACCAS. At seven weeks of age, mice were treated twice weekly with intraperitoneal RII6-C6 peptide. Experiments to find optimal dose were injected with 175μg per mouse, The treatment was stopped at 36 weeks of age. Mice were observed daily for clinical signs of disease and for mortality until the 40th week of age and were bled every two weeks for determination of anti-dsDNA and anti-ssDNA antibody titre; urine protein levels were determined in urine samples collected twice a week. Neither anti-dsDNA nor anti-ssDNA titres were significantly different in control and treated mice. Urine protein excretion was tested during the course of the treatment, Onset of proteinuria was significantly delayed (p<0.05) in the treated group and only 30% developed severe proteinuria, compared to 80% in the control group. The reduction in proteinuria in the treated group was accompanied by a striking increase in the survival rate. At the end of the treatment, 80% of RII6-C6 peptide-treated mice were still alive, whereas only 20% of the animals in the control groups survived. To determine whether treatment with RII6-C6 peptide led to histologically detectable changes, mice were examined for evidence of renal injury after treatment. Treatment with RII6-C6 peptide for 30 weeks significantly reduced mononuclear cells infiltration into the glomeruli and the deposition of IgG ICs, On the other hand, RII6-C6 peptide-treated mice showed no evidence of inflammatory disease, with only minimal mesangial expansion but essentially intact tubular architecture . Further confirmation of the ability of RII6-C6 peptide to prevent kidney damage was provided by detection of IgG deposits by immunostaining. Control mice showed deposition of glomerular ICs in kidney, whereas very slight ICs deposition was observed in RII6-C6 peptide-treated mice.
These results demonstrated that the RII6-C6 peptide in the context of this murine autoimmune disease was effective in delaying the onset of proteinuria, reducing kidney damage and improving survival, and thus could provide a basis for the development of FcR-targeting drugs.
为鉴定huFcγRII的线性结合表位,在EC2结构域设计合成huFcγRII多肽,偶联于载体蛋白BSA;以Dot-blot检测偶联多肽与人IgG的结合,并对阳性多肽进行进一步缺失分析。Dot-blot分析表明huFcγRII的151-163位多肽CTGNIGYTLFSSK是特异结合人IgG的有效多肽,为huFcγRII的线性结合表位,位于受体EC2结构域F-G环。含有huFcγRII线性结合表位的多肽不仅有效抑制人IgG与可溶性huFcγRII的结合,而且对huFcγRII转染细胞表面的IgG-FITC免疫荧光强度也具有良好的抑制功效,表明该结合表位多肽具有调节人IgG与细胞表面huFcγRII结合的能力,是首次发现的人FcR上存在线性结合表位。
为验证huFcγRII线性结合表位在体内的功能,将该多肽进行了动物实验。SLE小鼠模型实验表明该表位多肽提高了小鼠存活率,降低了严重蛋白尿比例和肾脏损伤程度,说明huFcγRII多肽对SLE模型小鼠的病情具有一定的延缓作用,对开发治疗自身免疫疾病的FcR靶标药物提供了参考。
Fc receptors are a group of important molecules expressed on the surface of immune accessory and effector cells, which bind the Fc region of immunoglobulins with specific affinities and have a number of important biological functions. FcRs play a crucial role in immune regulation by providing a link between the humoral and cellular responses. The antibody-mediated inflammatory response is regulated by activating and inhibitory FcRs. Thus, FcR-targeting provides therapies for allergy and autoimmune diseases. In this study using synthetic peptides we identified and characterized a linear epitope sequence in huFcγRII involved in the binding of human IgG. This is the first report describing linear epitopes on human FcRs capable of Fc-binding. This should further our understanding of the molecular mechanism of the FcγR-IgG interaction, and may provide a basis for the design of drugs with a potential for regulating antibody-mediated inflammation.
HuFcγRII is a low-affinity Fc receptor with two extracellular Ig-like domains and binds human IgG via the membrane proximal extracellular domain 2(EC2). To obtain a protein product equivalent to the extracellular domain of the huFcγRII, this domain of the huFcγRII gene was amplified from the recombinant plasmid ThuRII by PCR and then cloned into the pET-28a vector. The recombinant plasmid pETshuRII, after identification by PCR and double digestion, was transformed into E.coli BL21 (DE3). The results of SDS-PAGE showed that the molecular mass (M r) of the expressed protein was 24.8×103, and the expression rate was 30%.The washed inclusion bodies contained recombinant shuRII at up to 90% purity. The recombinant protein was dissolved in 6 M guanidine buffer, and then refolded by rapid dilution. ELISA showed that the refolded shuRII was able to bind human IgG in a dose dependent manner and using flow cytometry, that it competitively inhibited the binding of human IgG to huFcγRII expressed on the surface of COS-7 cells. These results demonstrate that it is possible to obtain large quantities of recombinant shuRII with comparable IgG binding properties to that of the whole membrane bound huFcγRII.
In order to express the receptor at the surface of a cultured cell, huFcγRII cDNA was cloned from human peripheral blood leucocytes by RT-PCR and a huFcγRII-expressing plasmid (pcDNA3-huFcγRII) was constructed. After verification by restriction digestion and PCR, the recombinant plasmid was transfected into COS-7 cells using lipofectamine. After screening by G418, a stable cell line expressing the receptor, identified by immunofluorescence and rosetting assays, was established. The result confirmed that the eukaryotic expression plasmid pcDNA3-huFcγRII was successfully constructed, and that the gene was transfected stably into COS-7 cells providing a solid experimental foundation for further investigation on the function of the huFcγRII gene.
To identify the linear epitope for Fc-binding on huFcγRII, peptides derived from the EC2 domain of huFcγRII were synthesized and coupled to BSA as carrier protein. Binding of human IgG to the different peptides was tested by Dot-blot assay. The effective peptide corresponding to the sequence 151-163 of huFcγRII located in the putative F-G loop of the EC2 domain possessed the ability to bind human IgG. The coupled peptide containing the IgG-binding epitope efficiently inhibited the binding of human IgG to soluble huFcγRII as well as to transfected COS-7 cells expressing huFcγRII. The Fc-binding epitope peptide showed the capability of modulating the interaction of IgG and huFcγRII on cell surface.
To study potential therapeutic properties of the peptide RII6-C6 in immune complex-mediated autoimmune disease, Female MRL/lpr mice (six weeks old) were purchased from SLACCAS. At seven weeks of age, mice were treated twice weekly with intraperitoneal RII6-C6 peptide. Experiments to find optimal dose were injected with 175μg per mouse, The treatment was stopped at 36 weeks of age. Mice were observed daily for clinical signs of disease and for mortality until the 40th week of age and were bled every two weeks for determination of anti-dsDNA and anti-ssDNA antibody titre; urine protein levels were determined in urine samples collected twice a week. Neither anti-dsDNA nor anti-ssDNA titres were significantly different in control and treated mice. Urine protein excretion was tested during the course of the treatment, Onset of proteinuria was significantly delayed (p<0.05) in the treated group and only 30% developed severe proteinuria, compared to 80% in the control group. The reduction in proteinuria in the treated group was accompanied by a striking increase in the survival rate. At the end of the treatment, 80% of RII6-C6 peptide-treated mice were still alive, whereas only 20% of the animals in the control groups survived. To determine whether treatment with RII6-C6 peptide led to histologically detectable changes, mice were examined for evidence of renal injury after treatment. Treatment with RII6-C6 peptide for 30 weeks significantly reduced mononuclear cells infiltration into the glomeruli and the deposition of IgG ICs, On the other hand, RII6-C6 peptide-treated mice showed no evidence of inflammatory disease, with only minimal mesangial expansion but essentially intact tubular architecture . Further confirmation of the ability of RII6-C6 peptide to prevent kidney damage was provided by detection of IgG deposits by immunostaining. Control mice showed deposition of glomerular ICs in kidney, whereas very slight ICs deposition was observed in RII6-C6 peptide-treated mice.
These results demonstrated that the RII6-C6 peptide in the context of this murine autoimmune disease was effective in delaying the onset of proteinuria, reducing kidney damage and improving survival, and thus could provide a basis for the development of FcR-targeting drugs.
引文
[1] ZHANG G P. Bovine IgG Fc Receptors [D]. Hatfield: University of Hertfordshire, 1994a.
[2] DAERON M. Fc receptor biology[J]. Annu Rev Immunol, 1997,15: 203-234.
[3] RAVETCH J V, BOLLAND S. IgG Fc receptors [J]. Annu Rev Immunol, 2001, 19: 275-290.
[4] COHEN-SOLAL J F, CASSARD L, FRIDMAN W H, et al. Fcγreceptors[J]. Immunol Lett, 2004, 92: 199-205.
[5] RAVETCH J V. Fc receptors[J]. Curr Opin Immunol,1997, 9: 121-125.
[6] BERKEN A, BENACERRAF B. Properties of antibodies cytophilic for macrophages[J]. J Exp Med, 1966, 123: 119-144.
[7] PARASKEVAS F, LEE S T, ORR K B, et al. A receptor for Fc on mouse B-lymphocytes[J]. J Immunol,1972, 108: 1319-1327.
[8] METZGER H, ALCARAZ G, HOHMAN R, et al. The receptor with high affinity for immunoglobulin E[J]. Annu Rev Immunol, 1986, 4: 419-470.
[9] WOOF J M and BURTON D R. Human antibody-Fc receptor interactions illuminated by crystal structures[J]. Nat Rev Immunol,2004, 4: 89-99.
[10] TAKAI T. Fc receptors and their role in immune regulation and autoimmunity[J]. J Clin Immunol, 2005, 25: 1-18.
[11] KACSKOVICS I. Fc receptors in livestock species[J]. Vet Immunol Immunopathol, 2004,102: 351-362.
[12] ALLEN J M, Seed B. Isolation and expression of functional high-affinity Fc receptor complementary DNAs[J]. Science, 1989, 243:378-381.
[13] BOLLAND S. A newly discovered Fc receptor that explains IgG-isotype disparities in effector responses[J]. Immunity, 2005, 23: 2-4.
[14] RAGHAVAN M, BJORKMAN P J. Fc receptors and their interactions with immunoglobulins[J]. Annu Rev Cell Dev. Biol, 1996, 12: 181-220.
[15] NIMMERJAHN F, BRUHNS P, HORIUCHI K, et al. FcγRIV: A novel FcR with distinct IgG subclass specificity[J]. Immunity, 2005, 23: 41-51.
[16] NIMMERJAHN F, RAVETCH J V. Divergent immunoglobulin G subclass activity throughselective Fc receptor binding[J]. Science, 2005, 31: 1510-1512 .
[17] JEFFERIS R, LUND J. Interaction sites on human IgG-Fc for FcR: current models[J]. Immnunol. Lett, 2002, 82 : 57-65.
[18] PASQUIER B, LAUNAY P, KANAMARU Y, et al. Identification of FcαRI as an inhibitory receptor that controls inflammation: dual role of FcRγITAM[J]. Immunity, 2005, 22: 31-42.
[19] RAVETCH J V, KINET J P. Fc receptors. Annu[J]. Rev Immunol, 1991, 9: 475-492.
[20] HULETT M D, HOGARTH P M. Molecular basis of Fc receptor function[J]. Adv Immunol, 1994, 57: 1-127.
[21] MECHETINA L V, NAJAKSHIN A M, ALABYEV B Y, et al. Identification of CD16-2, a novel mouse receptor homologous to CD16/Fc gamma RIII[J]. Immunogenetics, 2002, 54: 463-468.
[22] DAVIS R S, DENNIS G J, ODOM M R, et al. Fc receptor homologs: newest members of a remarkable diverse Fc receptor gene family[J]. Immunol Rev, 2002, 190: 123-136.
[23] SYMONS D B, CLARKSON C A. Genomic organisation and sequence of the extracellular domain exons of the bovine FcγRI receptor, and evidence for restricted binding of ruminant IgG to U937 cells[J]. Mol Immunol, 1992, 29: 1407-1413.
[24] YAN Y, LI X, ZHANG G P, et al. Molecular cloning and identification of full-length cDNA encoding high affinity Fc receptor for bovine IgG (FcγRI). Vet Immunol Immunopathol. 2000a,75: 151-159.
[25] ZHANG G, YOUNG J R, TREGASKES C R, et al.. Cattle Fc gamma RII: molecular cloning and ligand specificity[J]. Immunogenetics, 1994b, 39: 423–427.
[26] COLLINS R A, GELDER K I, HOWARD C J. Nucleotide sequence of cattle FcγRIII: its identification in gammadelta T cells[J]. Immunogenetics, 1997, 45: 440-443.
[27] YAN Y, ZHANG G, CHEN C, et al. Bovine FcγRIII with a single extracellular domain[J]. Res Vet Sci, 2000b, 68: 115-118.
[28] WATSON J L, JACKSON K A, KING D P, et al. Molecular cloning and sequencing of the low-affinity IgE receptor (CD23) for horse and cattle[J]. Vet Immunol Immunopathol, 2000, 73: 323-329.
[29] MORTON H C, PLEASS R J, STORSET A K, et al. Cloning and characterization of an immunoglobulin A Fc receptor from cattle[J]. Immunology, 2004a, 111: 204-211.
[30] ZHANG G P, YOUNG J R, TREGASKES C A, et al. Identification of a novel class of mammalian Fcγreceptor[J]. J Immunol, 1995, 155: 1534-1541.
[31] MORTON H C, STORSET A K, BRANDTZAEG P. Cloning and sequencing of a cDNA encoding the bovine FcRγchain[J]. Vet Immunol Immunopathol, 2001b, 82: 101-106.
[32] VERBEET M P, VERMEER H, WARMERDAM G C, et al. Cloning and characterization of the bovine polymeric immunoglobulin receptor-encoding cDNA[J]. Gene, 1995, 164: 329–333.
[33] KULSETH M A, KRAJCI P, MYKLEBOST O,et al. Cloning and characterization of two forms of bovine polymeric immunoglobulin receptor cDNA[J]. DNA Cell Biol, 1995, 14: 251–256.
[34] KACSKOVICS I, WU Z, SIMISTER N E, et al. Cloning and characterization of the bovine MHC class I-like Fc receptor[J]. J Immunol, 2000, 164: 1889-1897.
[35] MCALEESE S M, HALLIWELL R E, MILLER H R. Cloning and sequencing of the horse and sheep high-affinity IgE receptorαchain cDNA[J]. Immunogenetics, 2000, 51: 878-881.
[36] MCALEESE S M, MILLER H R. Cloning and sequencing of the equine and ovine high-affinity IgE receptorβ- andγ-chain cDNA[J]. Immunogenetics, 2003, 55: 122-125.
[37] MAYER B, ZOLNAI A, FRENYO L V, et al. Redistribution of the sheep neonatal Fc receptor in the mammary gland around the time of parturition in ewes and its localization in the small intestine of neonatal lambs[J]. Immunology, 2002, 107: 288–296.
[38] HALLORAN P J, SWEENEY S E, STROHMEIER C M, et al. Molecular cloning and identification of the porcine cytolytic trigger molecule G7 as a FcγRIIIα(CD16) homologue[J]. J Immunol, 1994, 153: 2631-2641.
[39] YIM D, JIE H B, LANIER L L, et al. Molecular cloning, gene structure, and expression pattern of pig immunoreceptor DAP12[J]. Immunogenetics, 2000, 51: 436-442.
[40] KUMURA B H, SONE T, SHIMAZAKI K, et al. Sequence analysis of porcine polymeric immunoglobulin receptor from mammary epithelial cells present in colostrum[J]. J Dairy Res, 2000, 67: 631–636.
[41] MORTON H C, PLEASS R J, STORSET A K, et al. Cloning and characterization of equineCD89 and identification of the CD89 gene in chimpanzees and rhesus macaques[J]. Immunology, 2005, 115: 74-84.
[42] FLESCH B K, NEPPERT J. Functions of the Fc receptors for immunoglobulin G[J]. J Clin Lab Anal, 2000, 14: 141-156.
[43] FOSSATI G, BUCKNALL R C, EDWARDS S W. Fcγreceptors in autoimmune diseases[J]. Eur J Clin Invest, 2001, 31: 821-831.
[44] HOGARTH P M. Fc receptors are major mediators of antibody based inflammation in autoimmunity[J]. Curr Opin Immunol, 2002, 14: 798-802.
[45] KLUNGLAND H, GOMEZ-RAYA L, HOWARD C J, et al. Mapping of bovine FcγR (FcγR) genes by sperm typing allows extended use of human map information[J]. Mamm Genome, 1997, 8: 573-577.
[46] SWEENEY S E, HALLORAN P J, KIM Y B. Identification of a unique porcine FcγRIIIAαmolecular complex[J]. Cell Immunol, 1996, 172: 92-99.
[47] QIAO S, ZHANG G P, XIA C, ZHANG H, et al. Cloning and characterization of porcine Fc gamma receptor II (FcγRII) [J]. Vet Immunol Immunopathol, 2006, 114: 178-184.
[48] ZHANG G P, QIAO S, LI Q, WANG X, et al. Molecular cloning and expression of the porcine high-affinity immunoglobulin G Fc receptor (FcγRI) [J]. Immunogenetics, 2006, 58: 845-849.
[49] KWIATKOWSKA K, SOBOTA A. The clustered Fcγreceptor II is recruited to Lyn-containing membrane domains and undergoes phosphorylation in a cholesterol-dependent manner[J]. Eur J Immunol, 2001, 31: 989-998.
[50] PRICOP L, REDECHA P, TEILLAUD J L,et al. Differential modulation of stimulatory and inhibitory Fcγreceptors on human monocytes by TH1 and TH2 cytokines[J]. J Immunol, 2001, 166: 531-537.
[51] MUTA T, KUROSAKI T, MISULOVIN Z, et al. A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell-receptor signalling[J]. Nature, 1994, 368: 70-73.
[52] TZENG S J, BOLLAND S, INABE K, et al. The B cell inhibitory Fc receptor triggers apoptosis by a novel c-Abl-family kinase dependent pathway[J]. J Biol Chem, 2005, 280: 35247–35254.
[53] RAVETCH J V, LANIER L. Immune inhibitory receptors[J]. Science, 2000, 290: 84–89.
[54] MCGAHA T L, SORRENTINO B, RAVETCH J V. Restoration of tolerance in lupus by targeted inhibitory receptor expression[J]. Science, 2005, 307: 590–593.
[55] BLANK MC, STEFANESCU RN, MASUDA E, et al. Decreased transcription of the human FCGR2B gene mediated by the-343 G/C promoter polymorphism and association with systemic lupus erythematosus[J]. Hum Genet, 2005, 117: 220–227.
[56] FUKUYAMA H, NIMMERJAHN F, RAVETCH J V. The inhibitory Fcgamma receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells[J]. Nat Immunol, 2005, 6: 99–106.
[57] OKAYAMA Y, KIRSHENBAUM A S, METCALFE D D. Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: up-regulation by IFN-gamma[J]. J Immunol, 2000,164: 4332–4339.
[58] RADEKE H H, JANSSEN-GRAALFS I, SOWA E N, et al. Opposite regulation of type II and III receptors for immunoglobulin G in mouse glomerular mesangial cells and in the induction of anti-glomerular basement membrane (GBM) nephritis[J]. J Biol Chem, 2002, 277: 27535–27544.
[59] TRIDANDAPANI S, WARDROP R, BARAN C P, et al. TGF-beta 1 suppresses [correction of supresses] myeloid Fc gamma receptor function by regulating the expression and function of the common gamma subunit[J]. J Immunol, 2003, 170: 4572–4577.
[60] GUYRE P M, MORGANELLI P M, MILLER R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes[J]. J Clin Invest, 1983, 72: 393–397.
[61] SHUSHAKOVA N, SKOKOWA J, SCHULMAN J, et al. C5a anaphylatoxin is a major regulator of activating versus inhibitory FcgammaRs in immune complex-induced lung disease[J]. J Clin Invest, 2002, 110: 1823–1830.
[62] GARCIA-GARCIA E, ROSALES C. Signal transduction during Fc receptor-mediated phagocytosis[J]. J Leukoc Biol, 2002, 72: 1092-1108.
[63] NAKAMURA A, AKIYAMA K, TAKAI T. Fc receptor targeting in the treatment of allergy, autoimmune diseases and cancer[J]. Expert Opin Ther Targets, 2005, 9: 169-190.
[64] VANLENT P, NABBE K C, BOROSS P, et al. The inhibitory receptor FcγRII reduces joint inflammation and destruction in experimental immune complex-mediated arthritides not onlyby inhibition of FcγRI/III but also by efficient clearance and endocytosis of immune complexes[J]. Am J Pathol, 2003, 163: 1839-1848.
[65] CLYNES R, TAKECHI Y, MOROI Y, et al. Fc receptors are required in passive and active immunity to melanoma[J]. Proc Natl Acad Sci, 1998a, 95: 652-656.
[66] CLYNES R A, TOWERS T L, PRESTA L G, et al. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets[J]. Nat. Med, 2000, 6: 443-446.
[67] TAKEDA K, YAMAGUCHI N, AKIBA H, et al. Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy[J]. J Exp Med, 2004, 199: 437-448.
[68] RODRIGUEZ A, REGNAULT A, KLEIJMEER M, et al. Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells[J]. Nat Cell Biol, 1999, 1: 362-368.
[69] AKIYAMA K, EBIHARA S, YADA A, et al. Targeting apoptotic tumor cells to Fc gamma R provides efficient and versatile vaccination against tumors by dendritic cells[J]. J Immunol, 2003, 170: 1641-1648.
[70] KALERGIS A M, RAVETCH J V. Inducing tumor immunity through the selective engagement of activating Fcγreceptors on dendritic cells[J]. J Exp Med, 2002, 195: 1653-1659.
[71] BORUCHOV A M, HELLER G, VERI M C, et al. Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions[J]. J Clin Invest, 2005, 115: 2914-2923.
[72] DHODAPKAR K M, KAUFMAN J L, EHLERS M, et al. Selective blockade of inhibitory Fcgamma receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells[J]. Proc Natl Acad Sci, 2005, 102: 2910–2915.
[73] SONDERMANN P, KAISER J, JACOB U. Molecular basis for immune complex recognition: a comparison of Fc-receptor structures[J]. J Mol Biol, 2001, 309: 737-749.
[74] SONDERMANN P, HUBER R, JACOB U. Crystal structure of the soluble form of the human Fcγ-receptor IIb: a new member of the immunoglobulin superfamily at 1.7 ? resolution[J]. EMBO J, 1999, 18: 1095-1103.
[75] SONDERMANN P, HUBER R, OOSTHUIZEN V, et al. The 3. 2-? crystal structure of the human IgG1 Fc fragment-FcγRIII complex[J]. Nature, 2000, 406: 267-273.
[76] ZHANG Y, BOESEN CC, RADAEV S, et al. Crystal structure of the extracellular domain ofa human FcγRIII[J]. Immunity, 2000, 13: 387-395.
[77] RADAEV S, MOTYKA S, FRIDMAN W H, et al. The structure of a human type III Fcγreceptor in complex with Fc[J]. J Biol Chem, 2001, 276: 16469-16477.
[78] GARMAN S C, KINET J P, JARDETZKY T S. Crystal structure of the human high-affinity IgE receptor[J]. Cell, 1998, 95: 951-961.
[79] GARMAN S C, WURZBURG B A, TARCHEVSKAYA S S, et al. Structure of the Fc fragment of human IgE bound to its high-affinity receptor FcεRIα[J]. Nature, 2000, 406: 259-266.
[80] GARMAN S C, SECHI S, KINET J P, et al. The analysis of the human high affinity IgE receptor FcεRIa from multiple crystal forms[J]. J Mol Boil, 2001, 311: 1049-1062.
[81] DING Y, XU G, YANG M, et al. Crystal Structure of the ectodomain of human FcαRI[J]. J Biol Chem, 2003, 278: 27966-27970.
[82] HERR A B, BALLISTER E R, BJORKMAN P J. Insights into IgA-mediated immune responses from the crystal structures of human FcαRI and its complex with IgA1-Fc[J]. Nature, 2003, 423: 614-620.
[83] RADAEV S, SUN P. Recognition of immunoglobulins by Fcγreceptors. Mol Immunol, 2001a, 38: 1073-1083.
[84] FAN Q R, MOSYAK L, WINTER C C, et al. Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors[J]. Nature, 1997, 389: 96-100.
[85] CHAPMAN T L, HEIKEMA A P, WEST A P, et al. Crystal structure and ligand binding properties of the D1D2 region of the inhibitory receptor LIR-1 (ILT2) [J]. Immunity, 2000, 13: 727-736.
[86] HULETT M D, HOGARTH P M. The second and third extracellular domains of FcγRI CD64) confer the unique high affinity binding of IgG2a[J]. Mol Immunol, 1998, 35: 989-996.
[87] HULETT M D, WITORT E, BRINKWORTH R I, et al. Identification of the IgG binding site of the human low affinity receptor for IgG FcγRII[J]. J Biol Chem,1994, 269: 15287-15293.
[88] HULETT M D, WITORT E, BRINKWORTH R I, et al. Multiple regions of human FcγRII (CD32) contribute to the binding of IgG[J]. J Biol Chem, 1995, 270: 21188-21194.
[89] TAMM A, KISTER A, NOLTE K U, et al. The IgG binding site of human FcγRIIIB receptorinvolves CC’and FG loops of the membrane-proximal domain[J]. J Biol Chem, 1996, 271: 3659-3666.
[90] DUNCAN A R, WOOF J M, PARTRIDGE L J, et al. Localization of the binding site for the human high-affinity Fc receptor on IgG[J]. Nature, 1988, 332: 563-564.
[91] CANFIELD S M, MORRISON S L. The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region[J]. J Exp Med, 1991, 173: 1483-1491.
[92] CHAPPEL M S, ISENMAN D E, EVERETT M, et al. Identification of the Fcγ-receptor class I binding site in human IgG through the use of recombinant IgG1/IgG2 hybrid and point-mutated antibodies[J]. Proc Natl Acad Sci, 1991, 88: 9036-9040.
[93] LUND J, WINTER G, JONES P T, et al. Human FcγRI and FcγRII interact with distinct but overlapping sites on human IgG[J]. J Immunol, 1991, 147: 2657-2662.
[94] HIBBS M L, TOLVANEN M, CARPEN O. Membrane-proximal Ig-like domain of FcγRIII (CD16) contains residues critical for ligand binding[J]. J Immunol, 1994, 152: 4466-4474.
[95] SHIELDS R L, NAMENUK A K, HONG K, et al. High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR[J]. J Biol Chem, 2001, 276: 6591-6604.
[96] RAVETCH J V, CLYNES R A. Divergent roles for Fc receptors and complement in vivo[J]. Annu Rev Immunol, 1998, 16: 421-432.
[97] NIMMERJAHN F. Activating and inhibitory FcγRs in autoimmune disorders[J]. Springer Semin Immunopathol, 2006, 28: 305–319.
[98] BOLLAND S, RAVETCH J V. Inhibitory pathways triggered by ITIM-containing receptors[J]. Adv Immunol, 1999, 72: 149–177.
[99] TAKAI T, LI M, SYLVESTRE D, et al. FcRγchain deletion results in pleiotrophic effector cell defects[J]. Cell, 1994, 76:519–529.
[100] CLYNES R, RAVETCH J V. Cytotoxic antibodies trigger in?ammation through Fc receptors[J]. Immunity, 1995, 3:21–26.
[101] CLYNES R, DUMITRU C, RAVETCH J V. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis[J]. Science, 1998, 279: 1052–1054.
[102] CLYNES R, MAIZES JS, GUINAMARD R, et al. Modulation of immune complex induced in?ammation in vivo by the coordinate expression of activation and inhibitory Fc receptors[J].J Exp Med, 1999, 189:179–186.
[103] PARK S Y, UEDA S, OHNO H, et al. Resistance of Fc receptor-deficient mice to fatal glomerulonephritis[J]. J Clin Invest, 1998, 102: 1229–1238.
[104] SUZUKI Y, SHIRATO I, OKUMURA K,et al. Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis[J]. Kidney Int , 1998, 54: 1166–1174.
[105] WATANABE N, AKIKUSA B, PARK S Y, et al. Mast cells induce autoantibody-mediated vasculitis syn-drome through tumor necrosis factor production upon triggering Fcγreceptors[J]. Blood, 1999, 94:3855–3863.
[106] HAZENBOS W L, GESSNER J E, HOFHUIS F M, et al. Impaired IgG-dependent anaphylaxis and Arthus reaction in FcγRIII (CD 16) deficient mice[J]. Immunity, 1996, 5: 181-188.
[107] HAZENBOS WLW, HEIJNEN IAFM, et al. Murine IgGl complexes trigger immune effector functions predominantly via FcγRIII (CD16) [J]. J Immunol, 1998, 161:3026-3032.
[108] DOMBROWICZ D, FLAMAND V, BRIGMAN K K, et al. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor a chain gene[J]. Cell, 1993, 75: 969-976.
[109] DOMBROWICZ D, FLAMAND V, MIYAJIMA I, et al. Absence of FcεRIαchain results in upregulation of FcγRIII-dependent mast cell degranulation and anaphylaxis. Evidence of competition between FcεRI and FcγRIII for limit-ing amounts of FcRβandγchain[J]. J Clin Invest, 1997, 99: 915–925.
[110] DOMBROWICZ D, LIN S, FLAMAND V, et al. Allergy-associated FcRβis a molecular amplifier of IgE- and IgG-mediated in vivo responses[J]. Immunity, 1998, 8:517-529.
[111] BARNES N, GAVIN A L, TAN P S, et al. FcγRI-deficient mice show multiple alterations to in?ammatory and immune responses[J]. Immunity, 2002, 16: 379-389.
[112] IOAN-FACSINAY A, DEKIMPE S J, HELLWIG S M, et al. FcγRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses and protection from bacterial infection[J]. Immunity, 2002, 16: 391- 402.
[113] YAMAGUCHI A, KATSUYAMA K, NAGAHAMA K, et al. Possible role of autoantibody in the pathophysiology of GM2 gangliosidoses[J]. J Clin Invest, 2004,113: 200-208.
[114] SYLVESTRE D L, RAVETCH J V. Fc receptors initiate the Arthus reaction: Redefining the in?ammatory cascade[J]. Science, 1994, 265: 1095-1098.
[115] GODAU J, HELLER T, HAWLISCH H, et al. C5a initiates the in?ammatory cascade in immune complex peritonitis[J]. J Immunol, 2004, 173: 3437-3445.
[116] JI H, OHMURA K, MAHMOOD U,et al. Arthritis critically dependent on innate immune system players[J]. Immunity, 2002, 16:157–168.
[117] SHUSHAKOVA N, SKOKOWA J, SCHULMAN J, et al. C5a anaphylatoxin is a major regulator of activating versus inhibitory FcγRs in immune complex-induced lung disease[J]. J Clin Invest, 2002, 110:1823-1830.
[118] RAVETCH J V. AMI complement of receptors in immune complex diseases[J]. J Clin Invest, 2002, 110:1759-1761.
[119] TRCKA J, MOROI Y, CLYNES R A, et al. Redundant and alternative roles for activating Fc receptors an complement in an antibody-dependent model of autoimmune vitiligo[J]. Immunity, 2002, 16:861-868.
[120] TAKAI T, ONO M, HIKIDA M, et al. Augmented humoral and anaphylactic responses in FcγRII-deficient mice[J]. Nature, 1996, 379:346-349.
[121] UJIKE A, ISHIKAWA Y, ONO M, et al. Modulation of IgE-mediated systemic anaphylaxis by low affinity Fc receptors for IgG[J]. J ExpMed, 1999, 189:1573-1579.
[122] SCHILLER C, JANSSEN-GRAALFS I, BAUMANN U, et al. Mouse FcγRII is a negative regulator of FcγRIII in IgG immune complex triggered in?ammation but not in autoantibody induced hemolysis[J]. Eur J Immunol, 2000, 30:481-490.
[123] ROOPENIAN D C, CHRISTIANSEN G J, SPROULE T J, et al. The MHCclass I-like IgGreceptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs[J]. J Immunol, 2003, 170:3528-3533.
[124] KLEINAU S, MARTINSSON P, HEYMAN B. Induction and suppression of collagen-induced arthritis is dependent on distinct Fcγreceptors[J]. J Exp Med, 2000, 191:1611-1616.
[125] NAKAMURA A, NUKIWA T, TAKAI T. Deregulation of peripheral B-cell development inenhanced severity of collagen-induced arthritis in FcγRIIB-deficient mice[J]. J Autoimmun 2003, 20:227-236.
[126] BOLLAND S, RAVETCH J V. Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis[J]. Immunity, 2000, 13:277-285.
[127] SAMUELSSON A, TOWERS T, RAVETCH J V. Anti-in?ammatory activity of IVIG mediated through the inhibitory Fc receptor[J]. Science, 2001, 291:484-486.
[128] YUASA T, KUBO S, YOSHINO T, et al. Deletion of FcγRIIB renders H-2b mice susceptible to collagen-induced arthritis[J]. J Exp Med, 1999, 189:187-194.
[129] NAKAMURA A, YUASA T, UJIKE A, et al. Fcγreceptor IIB-deficient mice develop Goodpasture’s syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease[J]. J Exp Med, 2000, 191:899-906.
[130] CLATWORTHY M R, SMIGH K G C. FcγRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis[J]. J Exp Med, 2004, 199:717-723.
[131] YU P, KOSCO-VILBOIS M, RICHARDS M, et al. Negative feedback regulation of IgE synthesis by murine CD23[J]. Nature, 1994, 369:753-756.
[132] ISRAEL E J, WILSKER D F, HAYES K C, et al. Increased clearance of IgG in mice that lackβ2-microglobulin: Possible protective role of FcRn[J]. Immunology, 1996, 89: 573-578.
[133] CHRISTIANSEN G J, BROOKS W, VEKASI S, et al.β2-Microglobulin-deficient mice are protected from hypergam maglobulinemia and have defective antibody responses because of increased IgG catabolism[J]. J Immunol, 1997, 159: 4781-4792.
[134] SHIMADA S, KAWAGUCHI-MIYASHITA M, KUSHIRO A, et al. Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA[J]. J Immunol, 1999, 163: 5367-5373.
[135] SONDERMANN P, OOSTHUIZEN V. The structure of Fc receptor/Ig complexes: considerations on stoichiometry and potential inhibitors[J]. Immunol Lett, 2002, 82: 51-56.
[136] NAKAMURA G R, STAROVASNIK M A, REYNOLDS M E, et al. A novel family of hairpin peptides that inhibit IgE activity by binding to the high-affinity IgE receptor[J]. Biochemistry, 2001, 40: 9828-9835.
[137] MARINO M, RUVO M, DE FALCO S, et al. Prevention of systemic lupus erythematosus in MRL/lpr mice by administration of an immunoglobulin-binding peptide[J]. Nat Biotechnol, 2000, 18: 735-739.
[138] SHERIDAN J M, HAYES G M, AUSTEN B M. Solid-phase synthesis and cyclization of a large branched peptide from IgG Fc with affinity for FcγRI[J]. J Pept Sci, 1999, 5: 555-562.
[139] URAY K, MEDGYESI D, HILBERT A, et al. Synthesis and receptor binding of IgG1 peptides derived from the IgG Fc region[J]. J Mol Recognit, 2004, 17: 95-105.
[140] ZHANG G P, GUO J Q, ZHOU J Y, et al. Identification of the linear epitope for Fc-binding on the bovine IgG2 Fc receptor (boFcγ2R) using synthetic peptides[J]. FEBS Letters, 2006, 580: 1383-1390.
[141] IERINO F L, POWELL M S, MCKENZIE I F, et al. Recombinant soluble human Fc gamma RII: production, characterization and inhibition of the Arthus reaction[J]. J Exp Med, 1993, 178(5): 1617-1628.
[142] WERWITZKE S, TRICK D, SONDERMANN P, et al. Treatment of Lupus-prone NZB/NZW F1 Mice with Recombinant Soluble FcγReceptor II (CD32) [J]. Ann Rheum Dis, 2008, 67(2): 154-161.
[143] BRINKLEY M A. A survey of methods for preparing protein conjugates with dyes, haptens and cross-linking reagents[J]. Bioconjugate Chem, 1992, 3:2-13.
[144] MATTSON G, CONKLIN E, DESAI S, et al. A practical approach to cross-linking[J]. Molecular Biology Reports, 1993, 17:167-183.
[145] SONDERMANN P, JACOB U. Human FcγRIIb expressed in Escherichia coli reveals IgG binding capability J]. Biol Chem, 1999, 380(6): 717-721.
[146] NASR A, ELGHAZALI G,GIHA H, et al. Interethnic differences in carriage of haemoglobin AS and Fcgamma receptor IIa (CD32) genotypes in children living in eastern Sudan[J]. Acta Trop, 2008,105:191-195.
[147] BROOKS D G, QIU W Q, LUSTER A D, et al. Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes[J]. J Exp Med,1989,170:1369-1385.
[148] STUART S G, SIMISTER N E,CLARKSON S B, et al. Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium[J]. EMBO J,1989,8:3657-3666.
[149] GUIRALDELLI M F, BERENSTEIN E H, GRODZKI A C, et al. The low affinity IgG receptor Fc gamma RIIB contributes to the binding of the mast cell specific antibody mAb BGD6[J]. Mol Immunol,2008, 45: 2411-2418.
[150] STENGELIN S, STAMENKOVIC I, SEED B. Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning[J]. EMBO J,1988,7:1053-1059.
[151] MEDGYESI D, URAY K, SALLAI K, et al. Functional mapping of the FcγRII binding site on human IgG1 by synthetic peptides[J]. Eur J Immunol, 2004, 34:1127-1135.
[152] MAXWELL K F, POWELL M S, HULETT M D, et al. Crystal structure of the human leukocyte Fc receptor, FcγRIIa[J]. Nat Struct Biol, 1999, 6: 437-442.
[153] KAISER E, COLESCOTT R L, BOSSINGER C D, et al. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides[J]. Anal Biochem, 1970, 34:595-598.
[154] VOJKOVSKY T. Detection of secondary amines on solid phase[J]. Pept Res, 1995, 8: 236-237.
[155] RIVIER J, MCCLINTOCK R, GALYEAN R, et al. Reversed-phase high-performance liquid chromatography: preparative purification of synthetic peptides[J]. J Chromatogr, 1984, 288: 303-328.
[156] QUIBELL D, JOHNSON T. Difficult peptides. In: Chan WC and White PD. Fmoc solid phase peptides synthesis: a practical approach[D]. New York: Oxford University Press, 2000.
[157] KATO K, SAUTES-FRIDMAN C, YAMADA W, et al. Structural basis of the interaction between IgG and Fcγreceptors[J]. J Mol Biol, 2000, 295: 213-224.
[158] THEOfiLOPOULOS A N, DIXON F J. Murine models of systemic lupus erythematosus[J]. Adv Immunol, 1985,37: 269–390.
[159] ANDREWS B S, EISENBERG R A, THEOfiLOPOULOS A N, et al. Spontaneous murine lupus-like syndromes: clinical and immunopathological manifestations in several strains[J]. J Exp Med, 1978,148: 1198-1215.
[160] REILLY C M, GILKESON G S. Use of genetic knockouts to modulate disease expression in a murine model of lupus, MRL/lpr mice[J]. Immunol Res, 2002, 25:143-153.
[161] EBLING F, HAHN B H. Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus. Comparison of antibodies in serum and renal eluates[J]. ArthritisRheum, 1980, 23: 392-403.
[162] MANNIK M. Pathophysiology of circulating immune complexes[J]. Arthritis Rheum, 1982, 25: 783-787.
[163] MEYER D, SCHILLER C, WESTERMANN J, et al. FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia[J]. Blood, 1998, 92: 3997-4002.
[164] CLYNES R, DUMITRU C, RAVETCH J V. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis[J]. Science, 1998b, 279:,1052-1064.
[165] WATANABE H, GARNIER G, CIRCOLO A, et al. Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B[J].J Immunol, 2000,164: 786-794.
[166] GAVIN A L, WINES B D, POWELL M S, et al. Recombinant soluble Fc gamma RII inhibits immune complex precipitation[J]. Clin Exp Immunol, 1995, 102: 620-625.
[167] WINES B D, GAVIN A, POWELL M S, et al. Soluble FcgammaRIIa inhibits rheumatoid factor binding to immune complexes[J]. Immunology, 2003, 109: 246-254.
[2] DAERON M. Fc receptor biology[J]. Annu Rev Immunol, 1997,15: 203-234.
[3] RAVETCH J V, BOLLAND S. IgG Fc receptors [J]. Annu Rev Immunol, 2001, 19: 275-290.
[4] COHEN-SOLAL J F, CASSARD L, FRIDMAN W H, et al. Fcγreceptors[J]. Immunol Lett, 2004, 92: 199-205.
[5] RAVETCH J V. Fc receptors[J]. Curr Opin Immunol,1997, 9: 121-125.
[6] BERKEN A, BENACERRAF B. Properties of antibodies cytophilic for macrophages[J]. J Exp Med, 1966, 123: 119-144.
[7] PARASKEVAS F, LEE S T, ORR K B, et al. A receptor for Fc on mouse B-lymphocytes[J]. J Immunol,1972, 108: 1319-1327.
[8] METZGER H, ALCARAZ G, HOHMAN R, et al. The receptor with high affinity for immunoglobulin E[J]. Annu Rev Immunol, 1986, 4: 419-470.
[9] WOOF J M and BURTON D R. Human antibody-Fc receptor interactions illuminated by crystal structures[J]. Nat Rev Immunol,2004, 4: 89-99.
[10] TAKAI T. Fc receptors and their role in immune regulation and autoimmunity[J]. J Clin Immunol, 2005, 25: 1-18.
[11] KACSKOVICS I. Fc receptors in livestock species[J]. Vet Immunol Immunopathol, 2004,102: 351-362.
[12] ALLEN J M, Seed B. Isolation and expression of functional high-affinity Fc receptor complementary DNAs[J]. Science, 1989, 243:378-381.
[13] BOLLAND S. A newly discovered Fc receptor that explains IgG-isotype disparities in effector responses[J]. Immunity, 2005, 23: 2-4.
[14] RAGHAVAN M, BJORKMAN P J. Fc receptors and their interactions with immunoglobulins[J]. Annu Rev Cell Dev. Biol, 1996, 12: 181-220.
[15] NIMMERJAHN F, BRUHNS P, HORIUCHI K, et al. FcγRIV: A novel FcR with distinct IgG subclass specificity[J]. Immunity, 2005, 23: 41-51.
[16] NIMMERJAHN F, RAVETCH J V. Divergent immunoglobulin G subclass activity throughselective Fc receptor binding[J]. Science, 2005, 31: 1510-1512 .
[17] JEFFERIS R, LUND J. Interaction sites on human IgG-Fc for FcR: current models[J]. Immnunol. Lett, 2002, 82 : 57-65.
[18] PASQUIER B, LAUNAY P, KANAMARU Y, et al. Identification of FcαRI as an inhibitory receptor that controls inflammation: dual role of FcRγITAM[J]. Immunity, 2005, 22: 31-42.
[19] RAVETCH J V, KINET J P. Fc receptors. Annu[J]. Rev Immunol, 1991, 9: 475-492.
[20] HULETT M D, HOGARTH P M. Molecular basis of Fc receptor function[J]. Adv Immunol, 1994, 57: 1-127.
[21] MECHETINA L V, NAJAKSHIN A M, ALABYEV B Y, et al. Identification of CD16-2, a novel mouse receptor homologous to CD16/Fc gamma RIII[J]. Immunogenetics, 2002, 54: 463-468.
[22] DAVIS R S, DENNIS G J, ODOM M R, et al. Fc receptor homologs: newest members of a remarkable diverse Fc receptor gene family[J]. Immunol Rev, 2002, 190: 123-136.
[23] SYMONS D B, CLARKSON C A. Genomic organisation and sequence of the extracellular domain exons of the bovine FcγRI receptor, and evidence for restricted binding of ruminant IgG to U937 cells[J]. Mol Immunol, 1992, 29: 1407-1413.
[24] YAN Y, LI X, ZHANG G P, et al. Molecular cloning and identification of full-length cDNA encoding high affinity Fc receptor for bovine IgG (FcγRI). Vet Immunol Immunopathol. 2000a,75: 151-159.
[25] ZHANG G, YOUNG J R, TREGASKES C R, et al.. Cattle Fc gamma RII: molecular cloning and ligand specificity[J]. Immunogenetics, 1994b, 39: 423–427.
[26] COLLINS R A, GELDER K I, HOWARD C J. Nucleotide sequence of cattle FcγRIII: its identification in gammadelta T cells[J]. Immunogenetics, 1997, 45: 440-443.
[27] YAN Y, ZHANG G, CHEN C, et al. Bovine FcγRIII with a single extracellular domain[J]. Res Vet Sci, 2000b, 68: 115-118.
[28] WATSON J L, JACKSON K A, KING D P, et al. Molecular cloning and sequencing of the low-affinity IgE receptor (CD23) for horse and cattle[J]. Vet Immunol Immunopathol, 2000, 73: 323-329.
[29] MORTON H C, PLEASS R J, STORSET A K, et al. Cloning and characterization of an immunoglobulin A Fc receptor from cattle[J]. Immunology, 2004a, 111: 204-211.
[30] ZHANG G P, YOUNG J R, TREGASKES C A, et al. Identification of a novel class of mammalian Fcγreceptor[J]. J Immunol, 1995, 155: 1534-1541.
[31] MORTON H C, STORSET A K, BRANDTZAEG P. Cloning and sequencing of a cDNA encoding the bovine FcRγchain[J]. Vet Immunol Immunopathol, 2001b, 82: 101-106.
[32] VERBEET M P, VERMEER H, WARMERDAM G C, et al. Cloning and characterization of the bovine polymeric immunoglobulin receptor-encoding cDNA[J]. Gene, 1995, 164: 329–333.
[33] KULSETH M A, KRAJCI P, MYKLEBOST O,et al. Cloning and characterization of two forms of bovine polymeric immunoglobulin receptor cDNA[J]. DNA Cell Biol, 1995, 14: 251–256.
[34] KACSKOVICS I, WU Z, SIMISTER N E, et al. Cloning and characterization of the bovine MHC class I-like Fc receptor[J]. J Immunol, 2000, 164: 1889-1897.
[35] MCALEESE S M, HALLIWELL R E, MILLER H R. Cloning and sequencing of the horse and sheep high-affinity IgE receptorαchain cDNA[J]. Immunogenetics, 2000, 51: 878-881.
[36] MCALEESE S M, MILLER H R. Cloning and sequencing of the equine and ovine high-affinity IgE receptorβ- andγ-chain cDNA[J]. Immunogenetics, 2003, 55: 122-125.
[37] MAYER B, ZOLNAI A, FRENYO L V, et al. Redistribution of the sheep neonatal Fc receptor in the mammary gland around the time of parturition in ewes and its localization in the small intestine of neonatal lambs[J]. Immunology, 2002, 107: 288–296.
[38] HALLORAN P J, SWEENEY S E, STROHMEIER C M, et al. Molecular cloning and identification of the porcine cytolytic trigger molecule G7 as a FcγRIIIα(CD16) homologue[J]. J Immunol, 1994, 153: 2631-2641.
[39] YIM D, JIE H B, LANIER L L, et al. Molecular cloning, gene structure, and expression pattern of pig immunoreceptor DAP12[J]. Immunogenetics, 2000, 51: 436-442.
[40] KUMURA B H, SONE T, SHIMAZAKI K, et al. Sequence analysis of porcine polymeric immunoglobulin receptor from mammary epithelial cells present in colostrum[J]. J Dairy Res, 2000, 67: 631–636.
[41] MORTON H C, PLEASS R J, STORSET A K, et al. Cloning and characterization of equineCD89 and identification of the CD89 gene in chimpanzees and rhesus macaques[J]. Immunology, 2005, 115: 74-84.
[42] FLESCH B K, NEPPERT J. Functions of the Fc receptors for immunoglobulin G[J]. J Clin Lab Anal, 2000, 14: 141-156.
[43] FOSSATI G, BUCKNALL R C, EDWARDS S W. Fcγreceptors in autoimmune diseases[J]. Eur J Clin Invest, 2001, 31: 821-831.
[44] HOGARTH P M. Fc receptors are major mediators of antibody based inflammation in autoimmunity[J]. Curr Opin Immunol, 2002, 14: 798-802.
[45] KLUNGLAND H, GOMEZ-RAYA L, HOWARD C J, et al. Mapping of bovine FcγR (FcγR) genes by sperm typing allows extended use of human map information[J]. Mamm Genome, 1997, 8: 573-577.
[46] SWEENEY S E, HALLORAN P J, KIM Y B. Identification of a unique porcine FcγRIIIAαmolecular complex[J]. Cell Immunol, 1996, 172: 92-99.
[47] QIAO S, ZHANG G P, XIA C, ZHANG H, et al. Cloning and characterization of porcine Fc gamma receptor II (FcγRII) [J]. Vet Immunol Immunopathol, 2006, 114: 178-184.
[48] ZHANG G P, QIAO S, LI Q, WANG X, et al. Molecular cloning and expression of the porcine high-affinity immunoglobulin G Fc receptor (FcγRI) [J]. Immunogenetics, 2006, 58: 845-849.
[49] KWIATKOWSKA K, SOBOTA A. The clustered Fcγreceptor II is recruited to Lyn-containing membrane domains and undergoes phosphorylation in a cholesterol-dependent manner[J]. Eur J Immunol, 2001, 31: 989-998.
[50] PRICOP L, REDECHA P, TEILLAUD J L,et al. Differential modulation of stimulatory and inhibitory Fcγreceptors on human monocytes by TH1 and TH2 cytokines[J]. J Immunol, 2001, 166: 531-537.
[51] MUTA T, KUROSAKI T, MISULOVIN Z, et al. A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell-receptor signalling[J]. Nature, 1994, 368: 70-73.
[52] TZENG S J, BOLLAND S, INABE K, et al. The B cell inhibitory Fc receptor triggers apoptosis by a novel c-Abl-family kinase dependent pathway[J]. J Biol Chem, 2005, 280: 35247–35254.
[53] RAVETCH J V, LANIER L. Immune inhibitory receptors[J]. Science, 2000, 290: 84–89.
[54] MCGAHA T L, SORRENTINO B, RAVETCH J V. Restoration of tolerance in lupus by targeted inhibitory receptor expression[J]. Science, 2005, 307: 590–593.
[55] BLANK MC, STEFANESCU RN, MASUDA E, et al. Decreased transcription of the human FCGR2B gene mediated by the-343 G/C promoter polymorphism and association with systemic lupus erythematosus[J]. Hum Genet, 2005, 117: 220–227.
[56] FUKUYAMA H, NIMMERJAHN F, RAVETCH J V. The inhibitory Fcgamma receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells[J]. Nat Immunol, 2005, 6: 99–106.
[57] OKAYAMA Y, KIRSHENBAUM A S, METCALFE D D. Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: up-regulation by IFN-gamma[J]. J Immunol, 2000,164: 4332–4339.
[58] RADEKE H H, JANSSEN-GRAALFS I, SOWA E N, et al. Opposite regulation of type II and III receptors for immunoglobulin G in mouse glomerular mesangial cells and in the induction of anti-glomerular basement membrane (GBM) nephritis[J]. J Biol Chem, 2002, 277: 27535–27544.
[59] TRIDANDAPANI S, WARDROP R, BARAN C P, et al. TGF-beta 1 suppresses [correction of supresses] myeloid Fc gamma receptor function by regulating the expression and function of the common gamma subunit[J]. J Immunol, 2003, 170: 4572–4577.
[60] GUYRE P M, MORGANELLI P M, MILLER R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes[J]. J Clin Invest, 1983, 72: 393–397.
[61] SHUSHAKOVA N, SKOKOWA J, SCHULMAN J, et al. C5a anaphylatoxin is a major regulator of activating versus inhibitory FcgammaRs in immune complex-induced lung disease[J]. J Clin Invest, 2002, 110: 1823–1830.
[62] GARCIA-GARCIA E, ROSALES C. Signal transduction during Fc receptor-mediated phagocytosis[J]. J Leukoc Biol, 2002, 72: 1092-1108.
[63] NAKAMURA A, AKIYAMA K, TAKAI T. Fc receptor targeting in the treatment of allergy, autoimmune diseases and cancer[J]. Expert Opin Ther Targets, 2005, 9: 169-190.
[64] VANLENT P, NABBE K C, BOROSS P, et al. The inhibitory receptor FcγRII reduces joint inflammation and destruction in experimental immune complex-mediated arthritides not onlyby inhibition of FcγRI/III but also by efficient clearance and endocytosis of immune complexes[J]. Am J Pathol, 2003, 163: 1839-1848.
[65] CLYNES R, TAKECHI Y, MOROI Y, et al. Fc receptors are required in passive and active immunity to melanoma[J]. Proc Natl Acad Sci, 1998a, 95: 652-656.
[66] CLYNES R A, TOWERS T L, PRESTA L G, et al. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets[J]. Nat. Med, 2000, 6: 443-446.
[67] TAKEDA K, YAMAGUCHI N, AKIBA H, et al. Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy[J]. J Exp Med, 2004, 199: 437-448.
[68] RODRIGUEZ A, REGNAULT A, KLEIJMEER M, et al. Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells[J]. Nat Cell Biol, 1999, 1: 362-368.
[69] AKIYAMA K, EBIHARA S, YADA A, et al. Targeting apoptotic tumor cells to Fc gamma R provides efficient and versatile vaccination against tumors by dendritic cells[J]. J Immunol, 2003, 170: 1641-1648.
[70] KALERGIS A M, RAVETCH J V. Inducing tumor immunity through the selective engagement of activating Fcγreceptors on dendritic cells[J]. J Exp Med, 2002, 195: 1653-1659.
[71] BORUCHOV A M, HELLER G, VERI M C, et al. Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions[J]. J Clin Invest, 2005, 115: 2914-2923.
[72] DHODAPKAR K M, KAUFMAN J L, EHLERS M, et al. Selective blockade of inhibitory Fcgamma receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells[J]. Proc Natl Acad Sci, 2005, 102: 2910–2915.
[73] SONDERMANN P, KAISER J, JACOB U. Molecular basis for immune complex recognition: a comparison of Fc-receptor structures[J]. J Mol Biol, 2001, 309: 737-749.
[74] SONDERMANN P, HUBER R, JACOB U. Crystal structure of the soluble form of the human Fcγ-receptor IIb: a new member of the immunoglobulin superfamily at 1.7 ? resolution[J]. EMBO J, 1999, 18: 1095-1103.
[75] SONDERMANN P, HUBER R, OOSTHUIZEN V, et al. The 3. 2-? crystal structure of the human IgG1 Fc fragment-FcγRIII complex[J]. Nature, 2000, 406: 267-273.
[76] ZHANG Y, BOESEN CC, RADAEV S, et al. Crystal structure of the extracellular domain ofa human FcγRIII[J]. Immunity, 2000, 13: 387-395.
[77] RADAEV S, MOTYKA S, FRIDMAN W H, et al. The structure of a human type III Fcγreceptor in complex with Fc[J]. J Biol Chem, 2001, 276: 16469-16477.
[78] GARMAN S C, KINET J P, JARDETZKY T S. Crystal structure of the human high-affinity IgE receptor[J]. Cell, 1998, 95: 951-961.
[79] GARMAN S C, WURZBURG B A, TARCHEVSKAYA S S, et al. Structure of the Fc fragment of human IgE bound to its high-affinity receptor FcεRIα[J]. Nature, 2000, 406: 259-266.
[80] GARMAN S C, SECHI S, KINET J P, et al. The analysis of the human high affinity IgE receptor FcεRIa from multiple crystal forms[J]. J Mol Boil, 2001, 311: 1049-1062.
[81] DING Y, XU G, YANG M, et al. Crystal Structure of the ectodomain of human FcαRI[J]. J Biol Chem, 2003, 278: 27966-27970.
[82] HERR A B, BALLISTER E R, BJORKMAN P J. Insights into IgA-mediated immune responses from the crystal structures of human FcαRI and its complex with IgA1-Fc[J]. Nature, 2003, 423: 614-620.
[83] RADAEV S, SUN P. Recognition of immunoglobulins by Fcγreceptors. Mol Immunol, 2001a, 38: 1073-1083.
[84] FAN Q R, MOSYAK L, WINTER C C, et al. Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors[J]. Nature, 1997, 389: 96-100.
[85] CHAPMAN T L, HEIKEMA A P, WEST A P, et al. Crystal structure and ligand binding properties of the D1D2 region of the inhibitory receptor LIR-1 (ILT2) [J]. Immunity, 2000, 13: 727-736.
[86] HULETT M D, HOGARTH P M. The second and third extracellular domains of FcγRI CD64) confer the unique high affinity binding of IgG2a[J]. Mol Immunol, 1998, 35: 989-996.
[87] HULETT M D, WITORT E, BRINKWORTH R I, et al. Identification of the IgG binding site of the human low affinity receptor for IgG FcγRII[J]. J Biol Chem,1994, 269: 15287-15293.
[88] HULETT M D, WITORT E, BRINKWORTH R I, et al. Multiple regions of human FcγRII (CD32) contribute to the binding of IgG[J]. J Biol Chem, 1995, 270: 21188-21194.
[89] TAMM A, KISTER A, NOLTE K U, et al. The IgG binding site of human FcγRIIIB receptorinvolves CC’and FG loops of the membrane-proximal domain[J]. J Biol Chem, 1996, 271: 3659-3666.
[90] DUNCAN A R, WOOF J M, PARTRIDGE L J, et al. Localization of the binding site for the human high-affinity Fc receptor on IgG[J]. Nature, 1988, 332: 563-564.
[91] CANFIELD S M, MORRISON S L. The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region[J]. J Exp Med, 1991, 173: 1483-1491.
[92] CHAPPEL M S, ISENMAN D E, EVERETT M, et al. Identification of the Fcγ-receptor class I binding site in human IgG through the use of recombinant IgG1/IgG2 hybrid and point-mutated antibodies[J]. Proc Natl Acad Sci, 1991, 88: 9036-9040.
[93] LUND J, WINTER G, JONES P T, et al. Human FcγRI and FcγRII interact with distinct but overlapping sites on human IgG[J]. J Immunol, 1991, 147: 2657-2662.
[94] HIBBS M L, TOLVANEN M, CARPEN O. Membrane-proximal Ig-like domain of FcγRIII (CD16) contains residues critical for ligand binding[J]. J Immunol, 1994, 152: 4466-4474.
[95] SHIELDS R L, NAMENUK A K, HONG K, et al. High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR[J]. J Biol Chem, 2001, 276: 6591-6604.
[96] RAVETCH J V, CLYNES R A. Divergent roles for Fc receptors and complement in vivo[J]. Annu Rev Immunol, 1998, 16: 421-432.
[97] NIMMERJAHN F. Activating and inhibitory FcγRs in autoimmune disorders[J]. Springer Semin Immunopathol, 2006, 28: 305–319.
[98] BOLLAND S, RAVETCH J V. Inhibitory pathways triggered by ITIM-containing receptors[J]. Adv Immunol, 1999, 72: 149–177.
[99] TAKAI T, LI M, SYLVESTRE D, et al. FcRγchain deletion results in pleiotrophic effector cell defects[J]. Cell, 1994, 76:519–529.
[100] CLYNES R, RAVETCH J V. Cytotoxic antibodies trigger in?ammation through Fc receptors[J]. Immunity, 1995, 3:21–26.
[101] CLYNES R, DUMITRU C, RAVETCH J V. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis[J]. Science, 1998, 279: 1052–1054.
[102] CLYNES R, MAIZES JS, GUINAMARD R, et al. Modulation of immune complex induced in?ammation in vivo by the coordinate expression of activation and inhibitory Fc receptors[J].J Exp Med, 1999, 189:179–186.
[103] PARK S Y, UEDA S, OHNO H, et al. Resistance of Fc receptor-deficient mice to fatal glomerulonephritis[J]. J Clin Invest, 1998, 102: 1229–1238.
[104] SUZUKI Y, SHIRATO I, OKUMURA K,et al. Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis[J]. Kidney Int , 1998, 54: 1166–1174.
[105] WATANABE N, AKIKUSA B, PARK S Y, et al. Mast cells induce autoantibody-mediated vasculitis syn-drome through tumor necrosis factor production upon triggering Fcγreceptors[J]. Blood, 1999, 94:3855–3863.
[106] HAZENBOS W L, GESSNER J E, HOFHUIS F M, et al. Impaired IgG-dependent anaphylaxis and Arthus reaction in FcγRIII (CD 16) deficient mice[J]. Immunity, 1996, 5: 181-188.
[107] HAZENBOS WLW, HEIJNEN IAFM, et al. Murine IgGl complexes trigger immune effector functions predominantly via FcγRIII (CD16) [J]. J Immunol, 1998, 161:3026-3032.
[108] DOMBROWICZ D, FLAMAND V, BRIGMAN K K, et al. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor a chain gene[J]. Cell, 1993, 75: 969-976.
[109] DOMBROWICZ D, FLAMAND V, MIYAJIMA I, et al. Absence of FcεRIαchain results in upregulation of FcγRIII-dependent mast cell degranulation and anaphylaxis. Evidence of competition between FcεRI and FcγRIII for limit-ing amounts of FcRβandγchain[J]. J Clin Invest, 1997, 99: 915–925.
[110] DOMBROWICZ D, LIN S, FLAMAND V, et al. Allergy-associated FcRβis a molecular amplifier of IgE- and IgG-mediated in vivo responses[J]. Immunity, 1998, 8:517-529.
[111] BARNES N, GAVIN A L, TAN P S, et al. FcγRI-deficient mice show multiple alterations to in?ammatory and immune responses[J]. Immunity, 2002, 16: 379-389.
[112] IOAN-FACSINAY A, DEKIMPE S J, HELLWIG S M, et al. FcγRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses and protection from bacterial infection[J]. Immunity, 2002, 16: 391- 402.
[113] YAMAGUCHI A, KATSUYAMA K, NAGAHAMA K, et al. Possible role of autoantibody in the pathophysiology of GM2 gangliosidoses[J]. J Clin Invest, 2004,113: 200-208.
[114] SYLVESTRE D L, RAVETCH J V. Fc receptors initiate the Arthus reaction: Redefining the in?ammatory cascade[J]. Science, 1994, 265: 1095-1098.
[115] GODAU J, HELLER T, HAWLISCH H, et al. C5a initiates the in?ammatory cascade in immune complex peritonitis[J]. J Immunol, 2004, 173: 3437-3445.
[116] JI H, OHMURA K, MAHMOOD U,et al. Arthritis critically dependent on innate immune system players[J]. Immunity, 2002, 16:157–168.
[117] SHUSHAKOVA N, SKOKOWA J, SCHULMAN J, et al. C5a anaphylatoxin is a major regulator of activating versus inhibitory FcγRs in immune complex-induced lung disease[J]. J Clin Invest, 2002, 110:1823-1830.
[118] RAVETCH J V. AMI complement of receptors in immune complex diseases[J]. J Clin Invest, 2002, 110:1759-1761.
[119] TRCKA J, MOROI Y, CLYNES R A, et al. Redundant and alternative roles for activating Fc receptors an complement in an antibody-dependent model of autoimmune vitiligo[J]. Immunity, 2002, 16:861-868.
[120] TAKAI T, ONO M, HIKIDA M, et al. Augmented humoral and anaphylactic responses in FcγRII-deficient mice[J]. Nature, 1996, 379:346-349.
[121] UJIKE A, ISHIKAWA Y, ONO M, et al. Modulation of IgE-mediated systemic anaphylaxis by low affinity Fc receptors for IgG[J]. J ExpMed, 1999, 189:1573-1579.
[122] SCHILLER C, JANSSEN-GRAALFS I, BAUMANN U, et al. Mouse FcγRII is a negative regulator of FcγRIII in IgG immune complex triggered in?ammation but not in autoantibody induced hemolysis[J]. Eur J Immunol, 2000, 30:481-490.
[123] ROOPENIAN D C, CHRISTIANSEN G J, SPROULE T J, et al. The MHCclass I-like IgGreceptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs[J]. J Immunol, 2003, 170:3528-3533.
[124] KLEINAU S, MARTINSSON P, HEYMAN B. Induction and suppression of collagen-induced arthritis is dependent on distinct Fcγreceptors[J]. J Exp Med, 2000, 191:1611-1616.
[125] NAKAMURA A, NUKIWA T, TAKAI T. Deregulation of peripheral B-cell development inenhanced severity of collagen-induced arthritis in FcγRIIB-deficient mice[J]. J Autoimmun 2003, 20:227-236.
[126] BOLLAND S, RAVETCH J V. Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis[J]. Immunity, 2000, 13:277-285.
[127] SAMUELSSON A, TOWERS T, RAVETCH J V. Anti-in?ammatory activity of IVIG mediated through the inhibitory Fc receptor[J]. Science, 2001, 291:484-486.
[128] YUASA T, KUBO S, YOSHINO T, et al. Deletion of FcγRIIB renders H-2b mice susceptible to collagen-induced arthritis[J]. J Exp Med, 1999, 189:187-194.
[129] NAKAMURA A, YUASA T, UJIKE A, et al. Fcγreceptor IIB-deficient mice develop Goodpasture’s syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease[J]. J Exp Med, 2000, 191:899-906.
[130] CLATWORTHY M R, SMIGH K G C. FcγRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis[J]. J Exp Med, 2004, 199:717-723.
[131] YU P, KOSCO-VILBOIS M, RICHARDS M, et al. Negative feedback regulation of IgE synthesis by murine CD23[J]. Nature, 1994, 369:753-756.
[132] ISRAEL E J, WILSKER D F, HAYES K C, et al. Increased clearance of IgG in mice that lackβ2-microglobulin: Possible protective role of FcRn[J]. Immunology, 1996, 89: 573-578.
[133] CHRISTIANSEN G J, BROOKS W, VEKASI S, et al.β2-Microglobulin-deficient mice are protected from hypergam maglobulinemia and have defective antibody responses because of increased IgG catabolism[J]. J Immunol, 1997, 159: 4781-4792.
[134] SHIMADA S, KAWAGUCHI-MIYASHITA M, KUSHIRO A, et al. Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA[J]. J Immunol, 1999, 163: 5367-5373.
[135] SONDERMANN P, OOSTHUIZEN V. The structure of Fc receptor/Ig complexes: considerations on stoichiometry and potential inhibitors[J]. Immunol Lett, 2002, 82: 51-56.
[136] NAKAMURA G R, STAROVASNIK M A, REYNOLDS M E, et al. A novel family of hairpin peptides that inhibit IgE activity by binding to the high-affinity IgE receptor[J]. Biochemistry, 2001, 40: 9828-9835.
[137] MARINO M, RUVO M, DE FALCO S, et al. Prevention of systemic lupus erythematosus in MRL/lpr mice by administration of an immunoglobulin-binding peptide[J]. Nat Biotechnol, 2000, 18: 735-739.
[138] SHERIDAN J M, HAYES G M, AUSTEN B M. Solid-phase synthesis and cyclization of a large branched peptide from IgG Fc with affinity for FcγRI[J]. J Pept Sci, 1999, 5: 555-562.
[139] URAY K, MEDGYESI D, HILBERT A, et al. Synthesis and receptor binding of IgG1 peptides derived from the IgG Fc region[J]. J Mol Recognit, 2004, 17: 95-105.
[140] ZHANG G P, GUO J Q, ZHOU J Y, et al. Identification of the linear epitope for Fc-binding on the bovine IgG2 Fc receptor (boFcγ2R) using synthetic peptides[J]. FEBS Letters, 2006, 580: 1383-1390.
[141] IERINO F L, POWELL M S, MCKENZIE I F, et al. Recombinant soluble human Fc gamma RII: production, characterization and inhibition of the Arthus reaction[J]. J Exp Med, 1993, 178(5): 1617-1628.
[142] WERWITZKE S, TRICK D, SONDERMANN P, et al. Treatment of Lupus-prone NZB/NZW F1 Mice with Recombinant Soluble FcγReceptor II (CD32) [J]. Ann Rheum Dis, 2008, 67(2): 154-161.
[143] BRINKLEY M A. A survey of methods for preparing protein conjugates with dyes, haptens and cross-linking reagents[J]. Bioconjugate Chem, 1992, 3:2-13.
[144] MATTSON G, CONKLIN E, DESAI S, et al. A practical approach to cross-linking[J]. Molecular Biology Reports, 1993, 17:167-183.
[145] SONDERMANN P, JACOB U. Human FcγRIIb expressed in Escherichia coli reveals IgG binding capability J]. Biol Chem, 1999, 380(6): 717-721.
[146] NASR A, ELGHAZALI G,GIHA H, et al. Interethnic differences in carriage of haemoglobin AS and Fcgamma receptor IIa (CD32) genotypes in children living in eastern Sudan[J]. Acta Trop, 2008,105:191-195.
[147] BROOKS D G, QIU W Q, LUSTER A D, et al. Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes[J]. J Exp Med,1989,170:1369-1385.
[148] STUART S G, SIMISTER N E,CLARKSON S B, et al. Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium[J]. EMBO J,1989,8:3657-3666.
[149] GUIRALDELLI M F, BERENSTEIN E H, GRODZKI A C, et al. The low affinity IgG receptor Fc gamma RIIB contributes to the binding of the mast cell specific antibody mAb BGD6[J]. Mol Immunol,2008, 45: 2411-2418.
[150] STENGELIN S, STAMENKOVIC I, SEED B. Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning[J]. EMBO J,1988,7:1053-1059.
[151] MEDGYESI D, URAY K, SALLAI K, et al. Functional mapping of the FcγRII binding site on human IgG1 by synthetic peptides[J]. Eur J Immunol, 2004, 34:1127-1135.
[152] MAXWELL K F, POWELL M S, HULETT M D, et al. Crystal structure of the human leukocyte Fc receptor, FcγRIIa[J]. Nat Struct Biol, 1999, 6: 437-442.
[153] KAISER E, COLESCOTT R L, BOSSINGER C D, et al. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides[J]. Anal Biochem, 1970, 34:595-598.
[154] VOJKOVSKY T. Detection of secondary amines on solid phase[J]. Pept Res, 1995, 8: 236-237.
[155] RIVIER J, MCCLINTOCK R, GALYEAN R, et al. Reversed-phase high-performance liquid chromatography: preparative purification of synthetic peptides[J]. J Chromatogr, 1984, 288: 303-328.
[156] QUIBELL D, JOHNSON T. Difficult peptides. In: Chan WC and White PD. Fmoc solid phase peptides synthesis: a practical approach[D]. New York: Oxford University Press, 2000.
[157] KATO K, SAUTES-FRIDMAN C, YAMADA W, et al. Structural basis of the interaction between IgG and Fcγreceptors[J]. J Mol Biol, 2000, 295: 213-224.
[158] THEOfiLOPOULOS A N, DIXON F J. Murine models of systemic lupus erythematosus[J]. Adv Immunol, 1985,37: 269–390.
[159] ANDREWS B S, EISENBERG R A, THEOfiLOPOULOS A N, et al. Spontaneous murine lupus-like syndromes: clinical and immunopathological manifestations in several strains[J]. J Exp Med, 1978,148: 1198-1215.
[160] REILLY C M, GILKESON G S. Use of genetic knockouts to modulate disease expression in a murine model of lupus, MRL/lpr mice[J]. Immunol Res, 2002, 25:143-153.
[161] EBLING F, HAHN B H. Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus. Comparison of antibodies in serum and renal eluates[J]. ArthritisRheum, 1980, 23: 392-403.
[162] MANNIK M. Pathophysiology of circulating immune complexes[J]. Arthritis Rheum, 1982, 25: 783-787.
[163] MEYER D, SCHILLER C, WESTERMANN J, et al. FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia[J]. Blood, 1998, 92: 3997-4002.
[164] CLYNES R, DUMITRU C, RAVETCH J V. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis[J]. Science, 1998b, 279:,1052-1064.
[165] WATANABE H, GARNIER G, CIRCOLO A, et al. Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B[J].J Immunol, 2000,164: 786-794.
[166] GAVIN A L, WINES B D, POWELL M S, et al. Recombinant soluble Fc gamma RII inhibits immune complex precipitation[J]. Clin Exp Immunol, 1995, 102: 620-625.
[167] WINES B D, GAVIN A, POWELL M S, et al. Soluble FcgammaRIIa inhibits rheumatoid factor binding to immune complexes[J]. Immunology, 2003, 109: 246-254.