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

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

作者机构：MOE/NHC Key Laboratory of Medical Molecular VirologySchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai200032China Central LaboratoryThe Second Affiliated Hospital of Fujian Medical UniversityQuanzhou362000China State Key Laboratory of Infectious Disease Prevention and ControlNational Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Shanghai Engineering Research Center for Synthetic ImmunologyShanghai200032China Shanghai Key Laboratory of Lung Inflammation and InjuryShanghai200032China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2022年第37卷第3期

页      面：370-379页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

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)。 

主　　题：Ig-seq HIV-1 Antibody repertoire VDJ rearrangement Junctional diversity 

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.