生发中心
断点群集区域
B细胞受体
细胞凋亡
细胞生物学
亲和力成熟
生物
信号转导
B细胞
癌症研究
化学
受体
抗体
免疫学
生物化学
作者
Takeshi Inoue,Yuma Matsumoto,Chie Kawai,Mao Ito,Shigeyuki Nada,Masato Okada,Tomohiro Kurosaki
摘要
Compared with naïve B cells, the B cell receptor (BCR) signal in germinal center (GC) B cells is attenuated; however, the significance of this signaling attenuation has not been well defined. Here, to investigate the role of attenuation of BCR signaling, we employed a Csk mutant mouse model in which Csk deficiency in GC B cells resulted in augmentation of net BCR signaling with no apparent effect on antigen presentation. We found that Csk is required for GC maintenance and efficient antibody affinity maturation. Mechanistically, ROS-induced apoptosis was exacerbated concomitantly with mitochondrial dysfunction in Csk-deficient GC B cells. Hence, our data suggest that attenuation of the BCR signal restrains hyper-ROS production, thereby protecting GC B cells from apoptosis and contributing to efficient affinity maturation.
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