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Volume 37 Issue 3
June 2022
    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
    shu

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

    • 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

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

        Corresponding author: Binbin Hong, bbh.0329@163.com
        Corresponding author: Liying Ma, mal@chinaaids.cn
        Corresponding author: Tianlei Ying, tlying@fudan.edu.cn
      • 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
      • 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.

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