title: Immunodominance of the VH1-46 antibody gene segment in the primary repertoire of human rotavirus-specific B cells is reduced in the memory compartment through somatic mutation of nondominant clones.
abstract: Detailed characterization of Ag-specific naive and memory B cell Ab repertoires elucidates the molecular basis for the generation of Ab diversity and the optimization of Ab structures that bind microbial Ags. In this study, we analyzed the immunophenotype and VH gene repertoire of rotavirus (RV) VP6-specific B cells in three circulating naive or memory B cell subsets (CD19+IgD+CD27-, CD19+IgD+CD27+, or CD19+IgD-CD27+) at the single-cell level. We aimed to investigate the influence of antigenic exposure on the molecular features of the two RV-specific memory B cell subsets. We found an increased frequency of CD19+IgD+CD27+ unclass-switched memory B cells and a low frequency of somatic mutations in CD19+IgD-CD27+ class-switched memory B cells in RV-specific memory B cells, suggesting a reduced frequency of isotype switching and somatic mutation in RV VP6-specific memory B cells compared with other memory B cells. Furthermore, we found that dominance of the VH1-46 gene segment was a prominent feature in the VH gene repertoire of RV VP6-specific naive B cells, but this dominance was reduced in memory B cells. Increased diversity in the VH gene repertoire of the two memory B cell groups derived from broader usage of VH gene segments, increased junctional diversity that was introduced by differential TdT activities, and somatic hypermutation.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232-2905, USA.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Tian
authors.forename: Grace K
authors.initials: GK
authors.lastname: Luskin
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Dischert
authors.forename: James N
authors.initials: JN
authors.lastname: Higginbotham
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000235:genetics / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D036022:Capsid Proteins / Q000276:immunology; D002999:Clone Cells; D018985:Epitopes, B-Lymphocyte / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics* / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics*; D008875:Middle Aged; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D012401:Rotavirus / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; C061332:VP6 protein, Rotavirus