Autoreactive B cells are silenced through receptor editing, clonal deletion and anergy induction. Additional autoreactive B cells are ignorant because of physical segregation from their cognate autoantigen. Unexpectedly, we find that follicular B cell-derived autoantigen, including cell surface molecules such as FcγRIIB, is a class of homeostatic autoantigen that can induce spontaneous germinal centers (GCs) and B cell-reactive autoantibodies in non-autoimmune animals with intact T and B cell repertoires. These B cell-reactive B cells form GCs in a manner dependent on spontaneous follicular helper T (T_FH) cells, which preferentially recognize B cell-derived autoantigen, and in a manner constrained by spontaneous follicular regulatory T (T_FR) cells, which also carry specificities for B cell-derived autoantigen. B cell-reactive GC cells are continuously generated and, following immunization or infection, become intermixed with foreign antigen-induced GCs. Production of plasma cells and antibodies derived from B cell-reactive GC cells are markedly enhanced by viral infection, potentially increasing the chance for autoimmunity. Consequently, immune homeostasis in healthy animals not only involves classical tolerance of silencing and ignoring autoreactive B cells but also entails a reactive equilibrium attained by a spontaneous B cell-reactive triad of B cells, T_FH cells and T_FR cells.

自身反应性 B 细胞通过受体编辑、克隆删除和无反应性诱导而被沉默。其他自身反应性 B 细胞由于与同源自身抗原的物理分离而无法识别。出乎意料的是，我们发现滤泡 B 细胞衍生的自身抗原，包括 FcγRIIB 等细胞表面分子，是一类稳态自身抗原，可以在具有完整 T 和 T 细胞的非自身免疫动物中诱导自发生发中心 (GC) 和 B 细胞反应性自身抗体。 B 细胞库。这些 B 细胞反应性 B 细胞以依赖于自发滤泡辅助 T (T _FH ) 细胞的方式形成 GC，该细胞优先识别 B 细胞衍生的自身抗原，并以受自发滤泡调节 T (T _FR ) 细胞限制的方式形成 GC。还具有 B 细胞衍生自身抗原的特异性。 B 细胞反应性 GC 细胞不断生成，并在免疫或感染后与外来抗原诱导的 GC 混合。病毒感染会显着增强 B 细胞反应性 GC 细胞产生的浆细胞和抗体，从而可能增加自身免疫的机会。因此，健康动物的免疫稳态不仅涉及对沉默和忽略自身反应性 B 细胞的经典耐受，而且还需要由 B 细胞、T _FH细胞和 T _FR细胞组成的自发 B 细胞反应三联体达到反应平衡。