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

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

来源：Nature Communications, 2015, 6(1): 6750.

DOI：10.1038/ncomms7750

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.

• 出版日期2015-4
• 单位河北医科大学