Department of Immunology, Duke University School of Medicine, Durham, NC, USA.
Duke University Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Immunol Rev. 2018 Jul;284(1):42-50. doi: 10.1111/imr.12661.
Germinal centers (GCs) are the primary sites of antibody affinity maturation, sites where B-cell antigen-receptor (BCR) genes rapidly acquire mutations and are selected for increasing affinity for antigen. This process of hypermutation and affinity-driven selection results in the clonal expansion of B cells expressing mutated BCRs and acts to hone the antibody repertoire for greater avidity and specificity. Remarkably, whereas the process of affinity maturation has been confirmed in a number of laboratories, models for how affinity maturation in GCs operates are largely from studies of genetically restricted B-cell populations competing for a single hapten epitope. Much less is known about GC responses to complex antigens, which involve both inter- and intraclonal competition for many epitopes. In this review, we (i) compare current methods for analysis of the GC B-cell repertoire, (ii) describe recent studies of GC population dynamics in response to complex antigens, discussing how the observed repertoire changes support or depart from the standard model of clonal selection, and (iii) speculate on the nature and potential importance of the large fraction of GC B cells that do not appear to interact with native antigen.
生发中心（GCs）是抗体亲和力成熟的主要部位，在此部位，B 细胞抗原受体（BCR）基因迅速获得突变，并通过选择来提高对抗原的亲和力。这种超突变和亲和力驱动的选择过程导致表达突变 BCR 的 B 细胞克隆扩增，并使抗体库具有更高的亲和力和特异性。值得注意的是，尽管亲和力成熟的过程已在多个实验室得到证实，但 GCs 中亲和力成熟的模型主要来自对竞争单个半抗原表位的遗传受限 B 细胞群体的研究。关于 GC 对复杂抗原的反应，人们知之甚少，因为它涉及到许多表位的种间和种内竞争。在这篇综述中，我们（i）比较了当前分析 GC B 细胞库的方法，（ii）描述了最近关于复杂抗原对 GC 群体动态的研究，讨论了观察到的库变化如何支持或偏离克隆选择的标准模型，以及（iii）推测与天然抗原不相互作用的大量 GC B 细胞的性质和潜在重要性。
