Mitochondrial function provides instructive signals for activation-induced B-cell fates

Kyoung Jin Jang, Hiroto Mano, Koji Aoki, Tatsunari Hayashi, Akihiko Muto, Yukiko Nambu, Katsu Takahashi, Katsuhiko Itoh, Shigeru Taketani, Stephen L. Nutt, Kazuhiko Igarashi, Akira Shimizu, Manabu Sugai

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Article number6750
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Apr 10
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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