State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Center for Precision Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Cell Rep. 2021 May 11;35(6):109110. doi: 10.1016/j.celrep.2021.109110.
Antibody repertoire sequencing enables researchers to acquire millions of B cell receptors and investigate these molecules at the single-nucleotide level. This power and resolution in studying humoral responses have led to its wide applications. However, most of these studies were conducted with a limited number of samples. Given the extraordinary diversity, assessment of these key features with a large sample set is demanded. Thus, we collect and systematically analyze 2,152 high-quality heavy-chain antibody repertoires. Our study reveals that 52 core variable genes universally contribute to more than 99% of each individual's repertoire; a distal interspersed preferences characterize V gene recombination; the number of public clones between two repertoires follows a linear model, and the positive selection dominates at RGYW motif in somatic hypermutations. Thus, this population-level analysis resolves some critical features of the antibody repertoire and may have significant value to the large cadre of scientists.
抗体库测序使研究人员能够获得数百万个 B 细胞受体，并在单核苷酸水平上研究这些分子。这种在体液免疫反应研究方面的强大功能和分辨率使其得到了广泛的应用。然而，这些研究大多是在有限数量的样本中进行的。鉴于抗体的多样性，需要使用大量样本集来评估这些关键特征。因此，我们收集并系统分析了 2152 个高质量的重链抗体库。我们的研究表明，52 个核心可变基因普遍为每个人的抗体库贡献了超过 99%的序列；远端散布的偏好特征决定了 V 基因的重组；两个抗体库之间的公共克隆数量遵循线性模型，而体细胞高频突变中的 RGYW 基序主要是阳性选择。因此，这种基于群体的分析解决了抗体库的一些关键特征，可能对广大科学家具有重要价值。
