Mitochondrial function provides instructive signals for activation-induced B-cell fates.
Mitochondrial function provides instructive signals for activation-induced B-cell fates.
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DOI：
10.1038/ncomms7750
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发表时间：
2015-04-10
影响因子：
16.6
通讯作者：
Sugai, Manabu
中科院分区：
文献类型：
--
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
在免疫反应中，功能不同的B细胞亚群是由随机过程产生的，包括类切换重组(CSR)和浆细胞分化(PCD)。在这项研究中，我们发现个体B细胞的命运与线粒体功能之间存在很强的相关性。CSR发生在激活的B细胞中，线粒体质量和膜电位增加，从而增加线粒体活性氧物种(MRO)，而PCD发生在线粒体质量和潜力降低的细胞中。这些事件是线粒体高B细胞群体中MRO最初轻微变化的结果。在CSR承诺的细胞中，MROS通过抑制亚铁离子与原卟啉IX的加成来减弱血红素的合成，从而维持Bach2的功能。减少的MRO然后通过增加血红素的合成来促进PCD。在PCD承诺的细胞中，Blimp1减少线粒体质量，从而降低MROS水平。将MROS确定为血色素合成调节剂可以增加对血液动态平衡调节机制的理解，以及B细胞激活后细胞命运的决定。细胞命运的选择通常基于噪声的放大。在这里，作者表明，线粒体活性氧物种的微小初始差异会导致线粒体质量和膜电位的较大变化，从而决定激活的B细胞对浆细胞的命运选择。
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. 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.
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影响因子：
4.8
作者：
Ochiai, Kyoko;Katoh, Yasutake;Igarashi, Kazuhiko
通讯作者：
Igarashi, Kazuhiko
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
100.3
作者：
Nutt, Stephen L.;Fairfax, Kirsten A.;Kallies, Axel
通讯作者：
Kallies, Axel
影响因子：
64.8
作者：
Reimold, AM;Iwakoshi, NN;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
56.9
作者：
Nambu, Y;Sugai, M;Shimizu, A
通讯作者：
Shimizu, A