Germinal centers and autoantibodies.,Immunology and Cell Biology

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Germinal centers and autoantibodies.
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2020-02-20 , DOI: 10.1111/imcb.12321
Clara Young _{1,

2} , Robert Brink _{1,

2}

Affiliation

Preventing self‐reactive lymphocytes from participating in effector responses is fundamental to maintaining immunological self‐tolerance and circumventing autoimmunity. A range of complementary mechanisms are known to act upon the primary B‐ and T‐cell repertoires to this effect, eliminating or silencing lymphocytes expressing self‐reactive antigen receptors generated through V(D)J recombination in early lymphoid precursors. In the case of B cells, secondary diversification of antigen receptor repertoire by somatic hypermutation (SHM) provides an additional challenge, especially because this occurs in germinal center (GC) B cells that are actively responding to antigen and primed for differentiation into antibody‐producing plasma cells. While it is clear that self‐tolerance mechanisms do act to prevent antibody production by self‐reactive GC B cells, it is also apparent that most pathogenic autoantibodies carry somatic mutations and so have derived from a GC response. Recent advances in the analysis of autoantibody‐producing cells associated with human autoimmune diseases together with insights gained from animal models have increased our understanding of the relationships between GCs, SHM and autoantibody production. Here we discuss these developments and focus in particular on how they have illuminated the genesis and pathogenesis of one archetypal autoantibody, rheumatoid factor.

中文翻译：

生发中心和自身抗体。

防止自身反应性淋巴细胞参与效应反应是维持免疫自我耐受和规避自身免疫的基础。已知一系列互补机制作用于初级 B 和 T 细胞库以达到这种效果，消除或沉默表达通过早期淋巴前体中 V(D)J 重组产生的自身反应性抗原受体的淋巴细胞。在 B 细胞的情况下，通过体细胞超突变 (SHM) 对抗原受体库的二次多样化提供了额外的挑战，特别是因为这发生在生发中心 (GC) B 细胞中，这些 B 细胞积极响应抗原并准备分化为产生抗体的细胞浆细胞。虽然很明显，自我耐受机制确实会阻止自我反应性 GC B 细胞产生抗体，但也很明显，大多数致病性自身抗体都带有体细胞突变，因此源自 GC 反应。分析与人类自身免疫疾病相关的自身抗体产生细胞的最新进展以及从动物模型中获得的见解，增加了我们对 GC、SHM 和自身抗体产生之间关系的理解。在这里，我们将讨论这些发展，并特别关注它们如何阐明一种原型自身抗体类风湿因子的发生和发病机制。分析与人类自身免疫疾病相关的自身抗体产生细胞的最新进展以及从动物模型中获得的见解，增加了我们对 GC、SHM 和自身抗体产生之间关系的理解。在这里，我们将讨论这些发展，并特别关注它们如何阐明一种原型自身抗体类风湿因子的发生和发病机制。分析与人类自身免疫疾病相关的自身抗体产生细胞的最新进展以及从动物模型中获得的见解，增加了我们对 GC、SHM 和自身抗体产生之间关系的理解。在这里，我们将讨论这些发展，并特别关注它们如何阐明一种原型自身抗体类风湿因子的发生和发病机制。

更新日期：2020-02-20

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