title: Deep sequencing and Circos analyses of antibody libraries reveal antigen-driven selection of Ig VH genes during HIV-1 infection.
abstract: The vast diversity of antibody repertoires is largely attributed to heavy chain (V(H)) recombination of variable (V), diversity (D) and joining (J) gene segments. We used 454 sequencing information of the variable domains of the antibody heavy chain repertoires from neonates, normal adults and an HIV-1-infected individual, to analyze, with Circos software, the VDJ pairing patterns at birth, adulthood and a time-dependent response to HIV-1 infection. Our comparative analyses of the Ig VDJ repertoires from these libraries indicated that, from birth to adulthood, VDJ recombination patterns remain the same with some slight changes, whereas some V(H) families are selected and preferentially expressed after long-term infection with HIV-1. We also demonstrated that the immune system responds to HIV-1 chronic infection by selectively expanding certain HV families in an attempt to combat infection. Our findings may have implications for understanding immune responses in pathology as well as for development of new therapeutics and vaccines.
authors.affiliation: Urbana High School, Ijamsville, MD 21754, USA; BSP CCR Genetics Core, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA; Werner H. Kirsten Student Intern Program, National Cancer Institute (NCI)-Frederick, National Institutes of Health (NIH), Frederick, MD 21702-1201, USA.
authors.forename: Madelyne
authors.initials: M
authors.lastname: Xiao
authors.forename: Ponraj
authors.initials: P
authors.lastname: Prabakaran
authors.forename: Weizao
authors.initials: W
authors.lastname: Chen
authors.forename: Bailey
authors.initials: B
authors.lastname: Kessing
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood / Q000235:genetics*; D005312:Fetal Blood / Q000276:immunology; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D007231:Infant, Newborn; D017422:Sequence Analysis, DNA; D012984:Software; D060152:V(D)J Recombination / Q000235:genetics
chemical_list: D000906:Antibodies; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region
keywords: 454 sequencing; Antibody repertoire; Antibodyome; HIV-1; Human monoclonal antibody; VDJ analysis