Large-Scale Analysis of 2,152 Dataset Reveals Key Features of B Cell Biology and the Antibody Repertoire

76 Pages Posted: 12 Nov 2019

See all articles by Xiujia Yang

Xiujia Yang

affiliation not provided to SSRN

Minhui Wang

affiliation not provided to SSRN

Dianchun Shi

affiliation not provided to SSRN

Yanfang Zhang

affiliation not provided to SSRN

Huikun Zeng

affiliation not provided to SSRN

Yan Zhu

affiliation not provided to SSRN

Chunhong Lan

affiliation not provided to SSRN

Jiaqi Wu

affiliation not provided to SSRN

Yang Deng

affiliation not provided to SSRN

Shixin Guo

affiliation not provided to SSRN

Lijun Xu

affiliation not provided to SSRN

Cuiyu Ma

affiliation not provided to SSRN

Yanxia Zhang

affiliation not provided to SSRN

Rongrong Wu

affiliation not provided to SSRN

Jinxia Ou

affiliation not provided to SSRN

Chu-jun Liu

affiliation not provided to SSRN

Changqing Chang

affiliation not provided to SSRN

Wei Yang

affiliation not provided to SSRN

Huijie Zhang

affiliation not provided to SSRN

Jun Chen

Zhejiang University

Liejie Qin

affiliation not provided to SSRN

Hongwei Zhou

affiliation not provided to SSRN

Jin-Xin Bei

affiliation not provided to SSRN

Lai Wei

affiliation not provided to SSRN

Guangwen Cao

Government of the People's Republic of China - Department of Epidemiology

Xueqing Yu

affiliation not provided to SSRN

Zhenhai Zhang

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.

Keywords: B-Cell Biology, Antibody Repertoire, Large-Scale Analysis, High-Throughput Sequencing, Ig-Seq

Suggested Citation

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

Xiujia Yang

affiliation not provided to SSRN

Minhui Wang

affiliation not provided to SSRN

Dianchun Shi

affiliation not provided to SSRN

Yanfang Zhang

affiliation not provided to SSRN

Huikun Zeng

affiliation not provided to SSRN

Yan Zhu

affiliation not provided to SSRN

Chunhong Lan

affiliation not provided to SSRN

Jiaqi Wu

affiliation not provided to SSRN

Yang Deng

affiliation not provided to SSRN

Shixin Guo

affiliation not provided to SSRN

Lijun Xu

affiliation not provided to SSRN

Cuiyu Ma

affiliation not provided to SSRN

Yanxia Zhang

affiliation not provided to SSRN

Rongrong Wu

affiliation not provided to SSRN

Jinxia Ou

affiliation not provided to SSRN

Chu-jun Liu

affiliation not provided to SSRN

Changqing Chang

affiliation not provided to SSRN

Wei Yang

affiliation not provided to SSRN

Huijie Zhang

affiliation not provided to SSRN

Jun Chen

Zhejiang University ( email )

School of Management
Zijingang Campus
Hangzhou, Zhejiang 310058
China

HOME PAGE: http://person.zju.edu.cn/junchen

Liejie Qin

affiliation not provided to SSRN

Hongwei Zhou

affiliation not provided to SSRN

Jin-Xin Bei

affiliation not provided to SSRN

Lai Wei

affiliation not provided to SSRN

Guangwen Cao

Government of the People's Republic of China - Department of Epidemiology ( email )

United States

Xueqing Yu

affiliation not provided to SSRN

Zhenhai Zhang (Contact Author)

Southern Medical University - State Key Laboratory of Organ Failure Research ( email )

Guangzhou, Guangdong Province
China

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