Department of Medicine, Division of Rheumatology, Immunology and Allergy Brigham and Women's Hospital and Harvard Medical School, USA.
Department of Medicine, Division of Rheumatology, Immunology and Allergy Brigham and Women's Hospital and Harvard Medical School, USA.
Curr Opin Immunol. 2019 Apr;57:32-39. doi: 10.1016/j.coi.2018.12.002. Epub 2019 Jan 25.
B cell immunoglobulin (Ig) repertoire composition shapes immune responses. The generation of Ig diversity begins with Ig variable region exon assembly from gene segments, random inter-segment junction sequence diversity, and combinations of Ig heavy and light chain. This generates vast preemptive sequence freedom in early developing B lineage cell Ig genes that can anticipate a great diversity of threats. This freedom is met with large restrictions that ultimately define the naïve (i.e. preimmune) Ig repertoire. Activation-induced somatic hypermutation (SHM), which further diversifies Ig V regions, is also met with strong selection that shapes Ig affinity maturation. While individual repertoire features, such as affinity for self and competition for foreign antigen, are known to drive selection, the selection filters themselves may be subject to regulation. Large sequence freedom coupled with strong selection for each diversification process provides flexibility for demand-driven regulation to dynamically balance antigen recognition capacities and associated autoimmune risks according to host needs.
B 细胞免疫球蛋白（Ig）库组成塑造免疫反应。Ig 多样性的产生始于 Ig 可变区外显子从基因片段组装、随机的片段间连接序列多样性，以及 Ig 重链和轻链的组合。这在早期发育的 B 细胞谱系 Ig 基因中产生了巨大的预先存在的序列自由度，可以预测到大量的威胁。这种自由度受到很大的限制，最终决定了幼稚（即先天）Ig 库。进一步使 Ig V 区多样化的激活诱导体细胞高频突变（SHM）也受到强烈的选择，从而塑造了 Ig 亲和力成熟。虽然已知个体库特征，如对自身的亲和力和对外来抗原的竞争，会驱动选择，但选择过滤器本身可能受到调节。每个多样化过程的大序列自由度加上对其的强烈选择为需求驱动的调节提供了灵活性，可以根据宿主的需要动态平衡抗原识别能力和相关的自身免疫风险。
