生发中心
生物
免疫球蛋白类转换
BCL6公司
抗体
免疫系统
体液免疫
免疫学
免疫
抗原
亲和力成熟
信号转导
细胞生物学
B细胞
作者
Yanchuan Li,Lele Zhu,Chun-Jung Ko,Jin-Young Yang,Hongjiao Wang,Ganiraju C. Manyam,Jing Wang,Xuhong Cheng,Shuli Zhao,Zuliang Jie
摘要
The formation of germinal centers (GCs) is crucial for humoral immunity and vaccine efficacy. Constant stimulation through microbiota drives the formation of constitutive GCs in Peyer’s patches (PPs), which generate B cells that produce antibodies against gut antigens derived from commensal bacteria and infectious pathogens. However, the molecular mechanism that regulates this persistent process is poorly understood. We report that Ewing Sarcoma Breakpoint Region 1 (EWSR1) is a brake to constitutive GC generation and immunoglobulin G (IgG) production in PPs, vaccination-induced GC formation, and IgG responses. Mechanistically, EWSR1 suppresses Bcl6 upregulation after antigen encounter, thereby negatively regulating induced GC B cell generation and IgG production. We further showed that tumor necrosis factor receptor-associated factor (TRAF) 3 serves as a negative regulator of EWSR1. These results established that the TRAF3–EWSR1 signaling axis acts as a checkpoint for Bcl6 expression and GC responses, indicating that this axis is a therapeutic target to tune GC responses and humoral immunity in infectious diseases.
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