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

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

62015-04-10 , Nature Publishing Group
機能的抗体産生を制御する活性化B細胞運命決定機構の解明 京都大学プレスリリース. 2015-04-14.
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.

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