Expression of essential B cell development genes in horses with common variable immunodeficiency
- 作者：R.L. Tallmadge rlt8@cornell.edu ; K.A. Such kimberlyasuch@gmail.com ; K.C. Miller kcm9@cornell.edu ; M.B. Matychak mbm10@cornell.edu ; M.J.B. Felippe ; mbf6@cornell.edu
- 关键词：cDNA ; complementary DNA ; CT ; cycle threshold ; CVID ; common variable immunodeficiency ; DNA ; deoxyribonucleic acid ; EDTA ; ethylenediaminetetraacetic acid ; mRNA ; messenger ribonucleic acid ; RNA ; ribonucleic acid ; RT-PCR ; reverse transcriptase polymerase chai
- 刊名：Molecular Immunology
- 出版年：2012
- 期刊代码：112_01615890
- 类别：bio
- 出版时间：June, 2012
- 卷：51
- 期：2
- 页码：169-176
- 文件大小：1306 K
摘要
Common variable immunodeficiency (CVID) is a heterogeneous disorder of B cell differentiation or function with inadequate antibody production. Our laboratory studies a natural form of CVID in horses characterized by late-onset B cell lymphopenia due to impaired B cell production in the bone marrow. This study was undertaken to assess the status of B cell differentiation in the bone marrow of CVID-affected horses by measuring the expression of genes essential for early B cell commitment and development. Standard RT-PCR revealed that most of the transcription factors and key signaling molecules that directly regulate B cell differentiation in the bone marrow and precede PAX5 are expressed in the affected horses. Yet, the expression of PAX5 and relevant target genes was variable. Quantitative RT-PCR analysis confirmed that the mRNA expression of E2A, PAX5, CD19, and IGHD was significantly reduced in equine CVID patients when compared to healthy horses (p < 0.05). In addition, the PAX5/EBF1 and PAX5/B220 ratios were significantly reduced in CVID patients (p < 0.01). Immunohistochemical analysis confirmed the absence of PAX5-BSAP expression in the bone marrow of affected horses. Our data suggest that B cell development seems to be impaired at the transition between pre-pro-B cells and pro-B cells in equine CVID patients.