Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis.
Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis.
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DOI：
10.1016/j.immuni.2018.04.031
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发表时间：
2018-06-19
期刊：
影响因子：
32.4
通讯作者：
Batista FD
中科院分区：
文献类型：
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作者：
Tsui C;Martinez-Martin N;Gaya M;Maldonado P;Llorian M;Legrave NM;Rossi M;MacRae JI;Cameron AJ;Parker PJ;Leitges M;Bruckbauer A;Batista FD
PKCβ缺失（Prkcb−/−）的小鼠严重免疫缺陷。在此我们表明，B细胞缺乏PKCβ的小鼠无法形成生发中心和浆细胞，这削弱了免疫应答中的亲和力成熟和抗体产生。此外，这些小鼠在病毒感染时无法产生浆细胞。在细胞水平上，我们已经表明Prkcb−/− B细胞表现出抗原极化和mTORC1信号传导缺陷。虽然改变的抗原极化损害了抗原呈递，并可能限制了生发中心发育的潜能，但有缺陷的mTORC1信号传导损害了这些细胞的代谢重编程、线粒体重塑和血红素生物合成，这些因素共同极大地阻碍了浆细胞分化。总之，我们的研究揭示了PKCβ作为B细胞极性和代谢重编程的关键调节因子指导B细胞命运的机制方面的见解。
B细胞中的PKCβ在体内促进生发中心应答和浆细胞分化
PKCβ调节B细胞中的抗原极化和抗原呈递
PKCβ驱动B细胞中的线粒体重塑和代谢重编程
代谢重编程与血红素积累相结合以指导效应细胞命运
淋巴细胞活化与代谢的重大变化相关。Tsui及其同事证明PKCβ促进代谢重编程以驱动B细胞中效应细胞命运的决定。
PKCβ-null (Prkcb−/−) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCβ failed to form germinal centers and plasma cells, which undermined affinity maturation and antibody production in response to immunization. Moreover, these mice failed to develop plasma cells in response to viral infection. At the cellular level, we have shown that Prkcb−/− B cells exhibited defective antigen polarization and mTORC1 signaling. While altered antigen polarization impaired antigen presentation and likely restricted the potential of GC development, defective mTORC1 signaling impaired metabolic reprogramming, mitochondrial remodeling, and heme biosynthesis in these cells, which altogether overwhelmingly opposed plasma cell differentiation. Taken together, our study reveals mechanistic insights into the function of PKCβ as a key regulator of B cell polarity and metabolic reprogramming that instructs B cell fate. PKCβ in B cells promotes GC response and plasma cell differentiation in vivo PKCβ regulates antigen polarization and antigen presentation in B cells PKCβ drives mitochondrial remodeling and metabolic reprogramming in B cells Metabolic reprogramming couples heme accumulation to instruct effector cell fate Lymphocyte activation is associated with major changes in metabolism. Tsui and colleagues demonstrate that PKCβ promotes metabolic reprogramming to drive effector fate decision in B cells.
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影响因子：
16.6
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
通讯作者：
Sugai, Manabu
影响因子：
64.8
作者：
Cunningham, John T.;Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
4.4
作者：
Garcia-Manteiga, Jose Manuel;Mari, Silvia;Sitia, Roberto
通讯作者：
Sitia, Roberto
影响因子：
4.4
作者：
Li, M;Davey, GM;Heath, WR
通讯作者：
Heath, WR
DOI：
10.1038/nri3804
发表时间：
2015-03
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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