生发中心
细胞生物学
B细胞
BCL6公司
亲和力成熟
补体系统
生物
B细胞受体
衰变加速因子
受体
CD40
分子生物学
补体受体
抗原
免疫学
抗体
生物化学
细胞毒性T细胞
体外
作者
Arun Čumpelik,Dávid Héja,Yuan Hu,Gabriele Varano,Farideh Ordikhani,Mark P. Roberto,Zhengxiang He,Dirk Homann,Sérgio A. Lira,David Dominguez-Sola,Peter S. Heeger
标识
DOI:10.1038/s41590-021-00926-0
摘要
Maturation of B cells within germinal centers (GCs) generates diversified B cell pools and high-affinity B cell antigen receptors (BCRs) for pathogen clearance. Increased receptor affinity is achieved by iterative cycles of T cell-dependent, affinity-based B cell positive selection and clonal expansion by mechanisms hitherto incompletely understood. Here we found that, as part of a physiologic program, GC B cells repressed expression of decay-accelerating factor (DAF/CD55) and other complement C3 convertase regulators via BCL6, but increased the expression of C5b-9 inhibitor CD59. These changes permitted C3 cleavage on GC B cell surfaces without the formation of membrane attack complex and activated C3a- and C5a-receptor signals required for positive selection. Genetic disruption of this pathway in antigen-activated B cells by conditional transgenic DAF overexpression or deletion of C3a and C5a receptors limited the activation of mechanistic target of rapamycin (mTOR) in response to BCR-CD40 signaling, causing premature GC collapse and impaired affinity maturation. These results reveal that coordinated shifts in complement regulation within the GC provide crucial signals underlying GC B cell positive selection.
科研通智能强力驱动
Strongly Powered by AbleSci AI