细胞生物学
生发中心
线粒体生物发生
葛兰素史克-3
细胞生长
生物
CD40
活性氧
化学
B细胞
线粒体
信号转导
生物化学
细胞毒性T细胞
免疫学
体外
抗体
作者
Julia Jellusova,Matthew H. Cato,John Apgar,Parham Ramezani-Rad,Charlotte R Leung,Cindi Chen,Adam Richardson,Elaine M. Conner,Robert J. Benschop,James R. Woodgett,Robert C. Rickert
摘要
B cells predominate in a quiescent state until an antigen is encountered, which results in rapid growth, proliferation and differentiation of the B cells. These distinct cell states are probably accompanied by differing metabolic needs, yet little is known about the metabolic control of B cell fate. Here we show that glycogen synthase kinase 3 (Gsk3) is a metabolic sensor that promotes the survival of naive recirculating B cells by restricting cell mass accumulation. In antigen-driven responses, Gsk3 was selectively required for regulation of B cell size, mitochondrial biogenesis, glycolysis and production of reactive oxygen species (ROS), in a manner mediated by the co-stimulatory receptor CD40. Gsk3 was required to prevent metabolic collapse and ROS-induced apoptosis after glucose became limiting, functioning in part by repressing growth dependent on the myelocytomatosis oncoprotein c-Myc. Notably, we found that Gsk3 was required for the generation and maintenance of germinal center B cells, which require high glycolytic activity to support growth and proliferation in a hypoxic microenvironment.
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