Abstract
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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Activating Transcription Factor 6 / genetics
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Activating Transcription Factor 6 / immunology
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Activating Transcription Factor 6 / metabolism*
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Animals
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Antibody-Producing Cells / immunology*
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism
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Endoplasmic Reticulum / genetics
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Endoplasmic Reticulum / immunology
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Endoplasmic Reticulum / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / immunology
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Protein Serine-Threonine Kinases / metabolism
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Regulatory Factor X Transcription Factors
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / immunology
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Transcription Factors / metabolism
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Unfolded Protein Response
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X-Box Binding Protein 1
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eIF-2 Kinase / genetics
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eIF-2 Kinase / immunology
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eIF-2 Kinase / metabolism
Substances
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Activating Transcription Factor 6
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Atf6 protein, mouse
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DNA-Binding Proteins
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Membrane Proteins
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Regulatory Factor X Transcription Factors
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Transcription Factors
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X-Box Binding Protein 1
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Xbp1 protein, mouse
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Ern2 protein, mouse
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PERK kinase
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Protein Serine-Threonine Kinases
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eIF-2 Kinase