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

查看全文 作　　者：Xiaolong [1]Tian;Binbin [2]Hong;Xiaoyi [1]Zhu;Desheng [3]Kong;Yumei [1]Wen;Yanling [1]Wu;Liying [3]Ma;Tianlei [1,4,5]Ying 机构地区：[1]MOE/NHC Key Laboratory of Medical Molecular Virology,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai,200032,China;[2]Central Laboratory,The Second Affiliated Hospital of Fujian Medical University,Quanzhou,362000,China;[3]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;[4]Shanghai Engineering Research Center for Synthetic Immunology,Shanghai,200032,China;[5]Shanghai Key Laboratory of Lung Inflammation and Injury,Shanghai,200032,China 出　　处：《Virologica Sinica》索引2022年第37卷第3期,共10页 基　　金：supported by grants from the National Key R&D Program of China(2019YFA0904400);National Natural Science Foundation of China(81822027,81630090,81902108);Science and Technology Commission of Shanghai Municipality(20DZ2254600,20DZ2261200)。 摘　　要：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. 关 键 词：Ig-seq HIV-1 Antibody repertoire VDJ rearrangement Junctional diversity