生发中心
三氯化碳
B细胞
生物
细胞生物学
否定选择
亲和力成熟
抗原
趋化因子
分子生物学
受体
免疫学
抗体
基因
遗传学
四氯化碳
基因组
作者
Fu Ke,Zachary Benet,Pavel V. Shelyakin,Olga V. Britanova,Neetu Gupta,Alexander L. Dent,Bethany B. Moore,Irina Grigorova
标识
DOI:10.1073/pnas.2304020121
摘要
Follicular regulatory T cells (Tfr) can play opposite roles in the regulation of germinal center (GC) responses. Depending on the studies, Tfr suppress or support GC and B cell affinity maturation. However, which factors determine positive vs. negative effects of Tfr on the GC B cell is unclear. In this study, we show that GC centrocytes that express MYC up-regulate expression of CCL3 chemokine that is needed for both the positive and negative regulation of GC B cells by Tfr. B cell–intrinsic expression of CCL3 contributes to Tfr-dependent positive selection of foreign Ag–specific GC B cells. At the same time, expression of CCL3 is critical for direct Tfr-mediated suppression of GC B cells that acquire cognate to Tfr nuclear proteins. Our study suggests that CCR5 and CCR1 receptors promote Tfr migration to CCL3 and highlights Ccr5 expression on the Tfr subset that expresses Il10 . Based on our findings and previous studies, we suggest a model of chemotactically targeted checkpoint control of B cells undergoing positive selection in GCs by Tfr, where Tfr directly probe and license foreign antigen–specific B cells to complete their positive selection in GCs but, at the same time, suppress GC B cells that present self-antigens cognate to Tfr.
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