Germinal centers (GCs) are the primary sites of clonal B cell expansion and affinity maturation, directing the production of high-affinity antibodies. This response is a central driver of pathogenesis in autoimmune diseases, such as systemic lupus erythematosus (SLE), but the natural history of autoreactive GCs remains unclear. Here, we present a novel mouse model where the presence of a single autoreactive B cell clone drives the TLR7-dependent activation, expansion, and differentiation of other autoreactive B cells in spontaneous GCs. Once tolerance was broken for one self-antigen, autoreactive GCs generated B cells targeting other self-antigens. GCs became independent of the initial clone and evolved toward dominance of individual clonal lineages, indicating affinity maturation. This process produced serum autoantibodies to a breadth of self-antigens, leading to antibody deposition in the kidneys. Our data provide insight into the maturation of the self-reactive B cell response, contextualizing the epitope spreading observed in autoimmune disease.

中文翻译：

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自身反应性生殖中心的克隆进化。

生殖中心（GC）是克隆B细胞扩增和亲和力成熟的主要部位，指导高亲和力抗体的产生。这种反应是自身免疫性疾病（例如系统性红斑狼疮（SLE））发病机理的主要驱动力，但自身反应性GC的自然史仍不清楚。在这里，我们介绍了一种新型的小鼠模型，其中单个自反应性B细胞克隆的存在驱动自发GC中其他自反应性B细胞的TLR7依赖性激活，扩增和分化。一旦打破了对一种自身抗原的耐受性，自动反应GC就会产生靶向其他自身抗原的B细胞。GC变得独立于最初的克隆，并朝着各个克隆谱系的优势发展，表明亲和力成熟。该过程产生了针对自身抗原广度的血清自身抗体，从而导致抗体在肾脏中沉积。我们的数据提供了对自我反应性B细胞反应成熟的洞察力，使自身免疫性疾病中观察到的抗原决定簇扩散具有相关性。