The specialized unfolded protein response of B lymphocytes: ATF6α-independent development of antibody-secreting B cells
| Autor: | Joseph W. Brewer, Suzanne Jackowski, Kazutoshi Mori, Robert A. Barrington, Ileana V. Aragon |
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| Rok vydání: | 2012 |
| Předmět: |
X-Box Binding Protein 1
XBP1 Immunology Regulatory Factor X Transcription Factors Protein Serine-Threonine Kinases Biology Endoplasmic Reticulum Article Mice eIF-2 Kinase Transcription (biology) Animals Secretion Antibody-Producing Cells Molecular Biology Transcription factor Cells Cultured B-Lymphocytes Endoplasmic reticulum Membrane Proteins Cell Differentiation Transmembrane protein Activating Transcription Factor 6 Cell biology DNA-Binding Proteins Mice Inbred C57BL Unfolded Protein Response Unfolded protein response Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | Molecular Immunology. 51:347-355 |
| ISSN: | 0161-5890 |
| Popis: | 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, IRE1α/β, PERK and ATF6α/β. 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, ATF6α 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 ATF6α-deficient B cells demonstrating that ATF6α 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. |
| Databáze: | OpenAIRE |
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