Southern Medical University - State Key Laboratory of Organ Failure Research
Date Written: Septemper 1, 2019
Abstract
Antibody repertoire sequencing (Ig-seq) has been widely used in studying humoral responses, with promising results. However, the promise of Ig-seq has not yet been fully realized, and key features of the antibody repertoire remain elusive or controversial. To clarify these key features, we analyzed 2,152 high-quality heavy chain antibody repertoires, representing 582 donors and a total of 360 million clones. Our study revealed that individuals exhibit very similar gene usage patterns for germline V, D, and J genes and that 53 core V genes contribute to more than 99% of the heavy chain repertoire. We further found that genetic background is sufficient but not necessary to determine usage of V, D, and J genes. Although gene usage pattern is not affected by age, we observed a significant sex preference for 24 V genes, 9 D genes and 5 J genes, but found no positional bias for V-D and D-J recombination. In addition, we found that the number of observed clones that were shared between any two repertoires followed a linear model and noted that the mutability of hot/cold spots and single nucleotides within antibody genes suggested a strand-specific somatic hypermutation mechanism. This population-level analysis resolves some critical characteristics of the antibody repertoire and thus may serve as a reference for research aiming to unravel B cell-related biology or diseases. The metrics revealed here will be of significant value to the large cadre of scientists who study the antibody repertoire.
Yang, Xiujia and Wang, Minhui and Shi, Dianchun and Zhang, Yanfang and Zeng, Huikun and Zhu, Yan and Lan, Chunhong and Wu, Jiaqi and Deng, Yang and Guo, Shixin and Xu, Lijun and Ma, Cuiyu and Zhang, Yanxia and Wu, Rongrong and Ou, Jinxia and Liu, Chu-jun and Chang, Changqing and Yang, Wei and Zhang, Huijie and Chen, Jun and Qin, Liejie and Zhou, Hongwei and Bei, Jin-Xin and Wei, Lai and Cao, Guangwen and Yu, Xueqing and Zhang, Zhenhai, Large-Scale Analysis of 2,152 Dataset Reveals Key Features of B Cell Biology and the Antibody Repertoire (Septemper 1, 2019). Available at SSRN: https://ssrn.com/abstract=3479006 or http://dx.doi.org/10.2139/ssrn.3479006
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