The specialized unfolded protein response of B lymphocytes: ATF6伪-independent development of antibody-secreting B cells

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• 作者：Ileana V. Aragon^a ; Robert A. Barrington^a ; Suzanne Jackowski^b ; Kazutoshi Mori^c ; Joseph W. Brewer^a ; ^{jbrewer@jaguar1.usouthal.edu}
• 关键词：ATF6 ; activating transcription factor 6 ; ER ; endoplasmic reticulum ; ERAD ; ER-associated degradation ; IRE1 ; inositol-requiring enzyme 1 ; KLH ; keyhole limpet hemocyanin ; MEFs ; mouse embryo fibroblasts ; NP ; nitrophenyl ; nt ; nucleotide ; PERK ; PKR-like ER kina
• 刊名：Molecular Immunology
• 出版年：2012
• 期刊代码：112_01615890
• 类别：bio
• 出版时间：July, 2012
• 卷：51
• 期：3-4
• 页码：347-355
• 文件大小：904 K

摘要

B lymphocytes, like all mammalian cells, are equipped with the unfolded protein response (UPR), a complex signaling system allowing for both pro- and mal-adaptive responses to increased demands on the endoplasmic reticulum (ER). The UPR is comprised of three signaling pathways initiated by the ER transmembrane stress sensors, IRE1伪/尾, PERK and ATF6伪/尾. Activation of IRE1 yields XBP1(S), a transcription factor that directs expansion of the ER and enhances protein biosynthetic and secretory machinery. XBP1(S) is essential for the differentiation of B lymphocytes into antibody-secreting cells. In contrast, the PERK pathway, a regulator of translation and transcription, is dispensable for the generation of antibody-secreting cells. Functioning as a transcription factor, ATF6伪 can augment ER quality control processes and drive ER expansion, but the potential role of this UPR pathway in activated B cells has not been investigated. Here, we report studies of ATF6伪-deficient B cells demonstrating that ATF6伪 is not required for the development of antibody-secreting cells. Thus, when B cells are stimulated to secrete antibody, a specialized UPR relies exclusively on the IRE1-XBP1 pathway to remodel the ER and expand cellular secretory capacity.