Characterization of human IgM and IgG repertoires in individuals with chronic HIV-1 infection

Xiaolong Tian; Binbin Hong; Xiaoyi Zhu; Desheng Kong; Yumei Wen; Yanling Wu; Liying Ma; Tianlei Ying

doi:10.1016/j.virs.2022.02.010

June 2022

Xiaolong Tian, Binbin Hong, Xiaoyi Zhu, Desheng Kong, Yumei Wen, Yanling Wu, Liying Ma and Tianlei Ying. Characterization of human IgM and IgG repertoires in individuals with chronic HIV-1 infection[J]. Virologica Sinica, 2022, 37(3): 370-379. doi: 10.1016/j.virs.2022.02.010

Citation: Xiaolong Tian, Binbin Hong, Xiaoyi Zhu, Desheng Kong, Yumei Wen, Yanling Wu, Liying Ma, Tianlei Ying. Characterization of human IgM and IgG repertoires in individuals with chronic HIV-1 infection .VIROLOGICA SINICA, 2022, 37(3) : 370-379. http://dx.doi.org/10.1016/j.virs.2022.02.010

基于高通量测序研究慢性HIV-1感染患者IgM及IgG抗体组库特征

田小龙 ^a ,
洪斌斌 ^b,, ,
朱晓艺 ^a ,
孔德生 ^c ,
闻玉梅 ^a ,
吴艳玲 ^a ,
马丽英 ^c,, ,
应天雷 ^a,d,e,,

a 复旦大学上海医学院基础医学院, 教育部/卫健委医学分子病毒学重点实验室, 中国, 上海, 200032;
b 福建医科大学第二附属医院中心实验室, 中国, 泉州, 362000;
c 中国疾病预防控制中心国家艾滋病/性病预防控制中心, 传染病预防控制国家重点实验室, 中国, 北京, 102206;
d 上海合成免疫工程技术研究中心, 中国, 上海, 200032;
e 上海市肺部炎症与损伤重点实验室, 中国, 上海, 200032

通讯作者： 洪斌斌, bbh.0329@163.com; 马丽英, mal@chinaaids.cn; 应天雷, tlying@fudan.edu.cn
收稿日期： 2021-09-25
录用日期： 2022-02-24

摘要

抗体组库在高通量测序上的进步前所未有地提高了我们大规模表征抗体组库的能力。然而，目前只有少数研究探讨了慢性HIV-1感染对人抗体组库的影响，而且受到测序深度和通量不足的限制出现了相互矛盾的结论。为了更好地了解HIV-1感染如何影响体液免疫系统，在本研究中，我们系统地分析了HIV-1感染患者的IgM （HIV-IgM）和IgG （HIV-IgG）重链抗体组库之间的差异，以及HIV-1患者和健康供体（HH）的IgM抗体组库之间的差异。结果发现，在HIV-IgM和HIV-IgG库中，共有的克隆占比极低，并且HIV-IgG中克隆的多样性显着降低，后者CDR1和CDR2的体细胞突变率高于前者。HIV-IgM中CDR3区域的平均长度显着长于HH库，这可能是由于前者中出现了大量新的VDJ重排模式，且对IGHJ6的偏好性使用。此外，一些B细胞克隆型中存在大量克隆，并且在HIV-IgG的克隆型谱系中检测到体细胞变异，表明其具有潜在的HIV-1中和活性。对HIV-IgG和HIV-IgM库的深入表征丰富了我们对HIV-1感染对人类抗体库的深远影响的认知，并可能对发现治疗性抗体具有实用价值。
- 抗体组学
- , 人类免疫缺陷病毒
- , VDJ基因重排
- , 连接区多样性

Characterization of human IgM and IgG repertoires in individuals with chronic HIV-1 infection

Xiaolong Tian ^a ,
Binbin Hong ^b,, ,
Xiaoyi Zhu ^a ,
Desheng Kong ^c ,
Yumei Wen ^a ,
Yanling Wu ^a ,
Liying Ma ^c,, ,
Tianlei Ying ^a,d,e,,

a MOE/NHC Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China;
b Central Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China;
c State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China;
d Shanghai Engineering Research Center for Synthetic Immunology, Shanghai, 200032, China;
e Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, 200032, China

Corresponding author: Binbin Hong, bbh.0329@163.com Liying Ma, mal@chinaaids.cn Tianlei Ying, tlying@fudan.edu.cn
Received Date: 25 September 2021
Accepted Date: 24 February 2022

Abstract

Advancements in high-throughput sequencing (HTS) of antibody repertoires (Ig-Seq) have unprecedentedly improved our ability to characterize the antibody repertoires on a large scale. However, currently, only a few studies explored the influence of chronic HIV-1 infection on human antibody repertoires and many of them reached contradictory conclusions, possibly limited by inadequate sequencing depth and throughput. To better understand how HIV-1 infection would impact humoral immune system, in this study, we systematically analyzed the differences between the IgM (HIV-IgM) and IgG (HIV-IgG) heavy chain repertoires of HIV-1 infected patients, as well as between antibody repertoires of HIV-1 patients and healthy donors (HH). Notably, the public unique clones accounted for only a negligible proportion between the HIV-IgM and HIV-IgG repertoires libraries, and the diversity of unique clones in HIV-IgG remarkably reduced. In aspect of somatic mutation rates of CDR1 and CDR2, the HIV-IgG repertoire was higher than HIV-IgM. Besides, the average length of CDR3 region in HIV-IgM was significant longer than that in the HH repertoire, presumably caused by the great number of novel VDJ rearrangement patterns, especially a massive use of IGHJ6. Moreover, some of the B cell clonotypes had numerous clones, and somatic variants were detected within the clonotype lineage in HIV-IgG, indicating HIV-1 neutralizing activities. The in-depth characterization of HIV-IgG and HIV-IgM repertoires enriches our knowledge in the profound effect of HIV-1 infection on human antibody repertoires and may have practical value for the discovery of therapeutic antibodies.
- Ig-seq
- , HIV-1
- , Antibody repertoire
- , VDJ rearrangement

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