China-Australia Centre for Personalised Immunology, Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
China-Australia Centre for Personalised Immunology, Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China; Francis Crick Institute, London, United Kingdom.
Adv Immunol. 2024;162:109-133. doi: 10.1016/bs.ai.2024.02.002. Epub 2024 Mar 6.
Spontaneously formed germinal centers (GCs) have been reported in most mouse models of human autoimmune disease and autoimmune patients, and have long been considered a source of somatically-mutated and thus high affinity autoantibodies, but their role in autoimmunity is becoming increasingly controversial, particularly in the context of systemic autoimmune diseases like lupus. On the one hand, there is good evidence that some pathogenic lupus antibodies have acquired somatic mutations that increase affinity for self-antigens. On the other hand, recent studies that have genetically prevented GC formation, suggest that GCs are dispensable for systemic autoimmunity, pointing instead to pathogenic extrafollicular (EF) B-cell responses. Furthermore, several lines of evidence suggest germinal centers may in fact be somewhat protective in the context of autoimmunity. Here we review how some of the conflicting evidence arose, and current views on the role of GCs in autoimmunity, outlining mechanisms by which GC may eliminate self-reactivity. We also discuss recent advances in understanding extrafollicular B cell subsets that participate in autoimmunity.
自发形成的生发中心（GC）已在大多数人类自身免疫性疾病的小鼠模型和自身免疫患者中被报道，长期以来一直被认为是体细胞突变和因此高亲和力自身抗体的来源，但其在自身免疫中的作用正变得越来越有争议，特别是在系统性自身免疫疾病如狼疮的背景下。一方面，有充分的证据表明，一些致病性狼疮抗体获得了增加对自身抗原亲和力的体细胞突变。另一方面，最近通过遗传方法阻止 GC 形成的研究表明，GC 对于系统性自身免疫是可有可无的，反而指向致病性滤泡外（EF）B 细胞反应。此外，有几条证据表明，生发中心在自身免疫的情况下实际上可能具有一定的保护作用。在这里，我们回顾了一些相互矛盾的证据是如何产生的，以及目前关于 GC 在自身免疫中的作用的观点，概述了 GC 可能消除自身反应的机制。我们还讨论了最近在理解参与自身免疫的滤泡外 B 细胞亚群方面的进展。
