In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions to limit autoimmune pathologies, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity.

中文翻译：

---

初始 B 细胞对自发生发中心的侵袭是快速且持久的

在由单个流氓 B 细胞克隆启动的自身反应性生发中心 (GC) 中，野生型 B 细胞扩增并产生针对其他自身抗原的克隆，称为表位扩散。表位扩散的慢性、渐进性要求早期干预以限制自身免疫病理，但野生型 B 细胞入侵和参与 GC 的动力学和分子要求仍然很大程度上未知。通过系统性红斑狼疮小鼠模型中的联体共生和过继转移方法，我们证明野生型 B 细胞可以快速加入现有的 GC，进行克隆扩展、持续存在，并有助于自身抗体的产生和多样化。野生型 B 细胞入侵自身反应性 GC 需要 TLR7、B 细胞受体特异性、抗原呈递和 I 型干扰素信号传导。过继转移模型提供了一种工具，用于识别自身免疫中 B 细胞耐受性破坏的早期事件。