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 CDRI 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 rear-rangement 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.

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

MOE/NHC Key Laboratory of Medical Molecular Virology,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai,200032,China;Central Laboratory,The Second Affiliated Hospital of Fujian Medical University,Quanzhou,362000,China;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;Shanghai Engineering Research Center for Synthetic Immunology,Shanghai,200032,China;Shanghai Key Laboratory of Lung Inflammation and Injury,Shanghai,200032,China

中国病毒学

[1]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)[J].中国病毒学,2022(03):370-379

repertoires,CDRI,CDR2,CDR3,VDJ,IGHJ6,clonotypes,clonotype

Characterization,human,IgM,IgG,individuals,chronic,HIV,infection,Advancements,throughput,sequencing,HTS,antibody,Seq,have,unprecedentedly,improved,our,ability,characterize,large,scale,However,currently,only,few,studies,explored,influence,many,them,reached,contradictory,conclusions,possibly,limited,by,inadequate,depth,To,better,understand,how,would,impact,humoral,immune,this,study,systematically,analyzed,differences,between,heavy,chain,infected,patients,well,healthy,donors,HH,Notably,public,unique,clones,accounted,negligible,proportion,libraries,diversity,remarkably,reduced,In,aspect,somatic,mutation,rates,was,higher,than,Besides,average,length,region,significant,longer,that,presumably,caused,great,number,novel,rear,rangement,patterns,especially,massive,Moreover,some,cell,had,numerous,variants,were,detected,within,lineage,indicating,neutralizing,activities,characterization,enriches,knowledge,profound,effect,may,practical,value,discovery,therapeutic,antibodies

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