Mitochondrial function provides instructive signals for activation-induced B-cell fates
Copyright policy )Mitochondrial function provides instructive signals for activation-induced B-cell fates
AbstractDuring 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 mitochondriahigh 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.
- University of Melbourne Australia
- Tohoku University Japan
- Kyoto University Japan
- University of Fukui Japan
- Walter and Eliza Hall Institute of Medical Research Australia
Male, Immunology, Plasma Cells, Primary Cell Culture, B-Lymphocyte Subsets, 610, Gene Expression, Protoporphyrins, Heme, Lymphocyte Activation, Article, Mice, Animals, Membrane Potential, Mitochondrial, Mice, Knockout, Cell Differentiation, Immunoglobulin Class Switching, Mitochondria, Mice, Inbred C57BL, Biological sciences, Basic-Leucine Zipper Transcription Factors, Cell Tracking, Positive Regulatory Domain I-Binding Factor 1, Reactive Oxygen Species
Male, Immunology, Plasma Cells, Primary Cell Culture, B-Lymphocyte Subsets, 610, Gene Expression, Protoporphyrins, Heme, Lymphocyte Activation, Article, Mice, Animals, Membrane Potential, Mitochondrial, Mice, Knockout, Cell Differentiation, Immunoglobulin Class Switching, Mitochondria, Mice, Inbred C57BL, Biological sciences, Basic-Leucine Zipper Transcription Factors, Cell Tracking, Positive Regulatory Domain I-Binding Factor 1, Reactive Oxygen Species
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