Department of Rheumatology and Inflammation Research, University of Gothenburg, PO Box 480, Gothenburg SE-405 30, Sweden.
Department of Microbiology and Immunology, University of Gothenburg, PO Box 435, Gothenburg SE-405 30, Sweden.
Nat Commun. 2015 May 11;6:7077. doi: 10.1038/ncomms8077.
Random recombination of antibody heavy- and light-chain genes results in a diverse B-cell receptor (BCR) repertoire including self-reactive BCRs. However, tolerance mechanisms that prevent the development of self-reactive B cells remain incompletely understood. The absence of the surrogate light chain, which assembles with antibody heavy chain forming a pre-BCR, leads to production of antinuclear antibodies (ANAs). Here we show that the naive follicular B-cell pool is enriched for cells expressing prototypic ANA heavy chains in these mice in a non-autoimmune background with a broad antibody repertoire. This results in the spontaneous formation of T-cell-dependent germinal centres that are enriched with B cells expressing prototypic ANA heavy chains. However, peripheral tolerance appears maintained by selection thresholds on cells entering the memory B-cell and plasma cell pools, as exemplified by the exclusion of cells expressing the intrinsically self-reactive V(H)81X from both pools.
抗体重链和轻链基因的随机重组导致了多样化的 B 细胞受体 (BCR) 库，其中包括自身反应性 BCR。然而，防止自身反应性 B 细胞发育的耐受机制仍不完全清楚。缺乏与抗体重链组装形成前 BCR 的替代轻链，会导致抗核抗体 (ANA) 的产生。在这里，我们发现在没有自身免疫的背景下，这些小鼠的幼稚滤泡 B 细胞池中富含表达原型 ANA 重链的细胞，并且具有广泛的抗体库。这导致了 T 细胞依赖性生发中心的自发形成，这些中心富含表达原型 ANA 重链的 B 细胞。然而，外周耐受似乎通过进入记忆 B 细胞和浆细胞池的细胞的选择阈值来维持，这表现在排除了同时表达内在自身反应性 V(H)81X 的细胞进入这两个池。
