The adaptive immune system is tasked with producing antibodies that recognize a wide scope of potential pathogens, including those never before encountered, and concurrently avoiding formation of antibodies binding host tissues. The diverse repertoire of antibodies produced by V(D)J recombination inevitably includes autoantibodies that bind to self-antigens, estimated to be as much as 70% of nascent antibodies on immature B cells. Early theoretical models of tolerance hypothesized that such self-reactive clones could not possibly be allowed to survive and mature. However from the first direct view of the fate of nascent B cells carrying a self-binding antibody it was clear that many "forbidden clones" circulate to secondary lymphoid tissues, where they adopt an IgMlow IgD+ cell surface phenotype and are prevented from secreting autoantibodies by a series of tolerance checkpoints referred to as "clonal anergy." Since anergic B cells can be reactivated to secrete pathogenic autoantibodies in certain settings, the advantage of controlling self-reactive antibodies by clonal anergy has until recently remained enigmatic. Here we review this topic and recent advances showing that anergic B cells are recruited into the germinal center to mutate away from self-reactivity, undergoing "clonal redemption" into cells making antibodies with exquisite specificity for foreign immunogens.

中文翻译：

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克隆赎回和克隆无能为平衡B细胞耐受性和免疫力的机制。

适应性免疫系统的任务是产生识别广泛潜在病原体（包括从未遇到过的病原体）的抗体，并同时避免形成与宿主组织结合的抗体。由V（D）J重组产生的抗体的多样性库中不可避免地包括与自身抗原结合的自身抗体，据估计，这种抗体约占未成熟B细胞新生抗体的70％。早期的耐受性理论模型假设，这种自我反应性克隆不可能生存和成熟。但是，从直接携带带有自结合抗体的新生B细胞的命运的第一个直接角度来看，很明显，许多“禁止克隆”循环到次级淋巴组织，他们采用IgMlow IgD +细胞表面表型，并通过一系列称为“克隆无反应性”的耐受性检查点阻止分泌自身抗体。由于可以在某些情况下重新激活无反应性B细胞以分泌病原性自身抗体，因此直到最近，通过克隆无能控制自身反应性抗体的优势一直不为人知。在这里，我们回顾了这个话题，最近的进展表明，无能的B细胞被募集到生发中心以突变远离自身反应性，经历“克隆性赎回”，形成了对外源免疫原具有极高特异性的抗体。直到最近，通过克隆无反应来控制自身反应性抗体的优势仍然是个谜。在这里，我们回顾这个话题和最近的进展，表明无能的B细胞被募集到生发中心以突变远离自身反应性，经历“克隆救赎”进入细胞，从而产生对外源免疫原具有极高特异性的抗体。直到最近，通过克隆无反应来控制自身反应性抗体的优势仍然是个谜。在这里，我们回顾了这个话题，最近的进展表明，无能的B细胞被募集到生发中心以突变远离自身反应性，经历“克隆性赎回”，形成了对外源免疫原具有极高特异性的抗体。