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Mitochondrial function provides instructive signals for activation-induced B-cell fates
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Journal Article
Mitochondrial function provides instructive signals for activation-induced B-cell fates
2015
Overview
During immune reactions, functionally distinct B-cell subsets are generated by stochastic processes, including class-switch recombination (CSR) and plasma cell differentiation (PCD). In this study, we show a strong association between individual B-cell fates and mitochondrial functions. CSR occurs specifically in activated B cells with increased mitochondrial mass and membrane potential, which augment mitochondrial reactive oxygen species (mROS), whereas PCD occurs in cells with decreased mitochondrial mass and potential. These events are consequences of initial slight changes in mROS in mitochondria
high
B-cell populations. In CSR-committed cells, mROS attenuates haeme synthesis by inhibiting ferrous ion addition to protoporphyrin IX, thereby maintaining Bach2 function. Reduced mROS then promotes PCD by increasing haeme synthesis. In PCD-committed cells, Blimp1 reduces mitochondrial mass, thereby reducing mROS levels. Identifying mROS as a haeme synthesis regulator increases the understanding of mechanisms regulating haeme homeostasis and cell fate determination after B-cell activation.
Cell fate choices are often based on amplification of noise. Here the authors show that small initial differences in mitochondrial reactive oxygen species lead to bigger changes in mitochondrial mass and membrane potential, which then determine plasma cell fate choice of activated B cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
Subject
/ 38/1
/ 42
/ 42/35
/ 82
/ Animals
/ Antigens
/ B-Lymphocyte Subsets - cytology
/ B-Lymphocyte Subsets - immunology
/ B-Lymphocyte Subsets - metabolism
/ Basic-Leucine Zipper Transcription Factors - deficiency
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Cells
/ Humanities and Social Sciences
/ Immunoglobulin Class Switching - genetics
/ Male
/ Medicine
/ Membrane Potential, Mitochondrial - immunology
/ Mice
/ Plasma
/ Positive Regulatory Domain I-Binding Factor 1
/ Protoporphyrins - metabolism
/ Reactive Oxygen Species - immunology
/ Reactive Oxygen Species - metabolism
/ Science
