title: VH1-46 is the dominant immunoglobulin heavy chain gene segment in rotavirus-specific memory B cells expressing the intestinal homing receptor alpha4beta7.
abstract: Memory B cells expressing the intestinal homing marker alpha4beta7 are important for protective immunity against human rotavirus (RV). It is not known whether the B cell repertoire of intestinal homing B cells differs from B cells of the systemic compartment. In this study, we analyzed the RV-specific VH and VL repertoire in human IgD- B cells expressing the intestinal homing marker alpha4beta7. The mean frequency of RV-specific B cells in the systemic compartment of healthy adult subjects was 0.6% (range, 0.2-1.2). The mean frequency of IgD- B cells that were both RV specific and alpha4beta7 was 0.04% (range, 0.01-0.1), and a mean of 10% (range, 1-32) of RV-specific peripheral blood human B cells exhibited an intestinal homing phenotype. We previously demonstrated that VH1-46 is the dominant Ab H chain gene segment in RV-specific systemic B cells from adults and infants. RV-specific systemic IgD- or intestinal homing IgD-/alpha4beta7+ B cells in the current study also used the gene segment VH1-46 at a high frequency, while randomly selected B cells with those phenotypes did not. These data show that VH1-46 is the immunodominant gene segment in human RV-specific effector B cells in both the systemic compartment and in intestinal homing lymphocytes. The mean replacement/silent mutation ratio of systemic compartment IgD- B cells was >2, consistent with a memory phenotype and antigenic selection. Interestingly, RV-specific intestinal homing IgD-/alpha4beta7+ B cells using the VH1-46 gene segment were not mutated, in contrast to systemic RV-specific IgD- B cells.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Jörn-Hendrik
authors.initials: JH
authors.lastname: Weitkamp
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Kallewaard
authors.forename: Amber L
authors.initials: AL
authors.lastname: Bowen
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: Lafleur
authors.forename: Harry B
authors.initials: HB
authors.lastname: Greenberg
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D001782:Blood Donors; D002999:Clone Cells; D005803:Genes, Immunoglobulin; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism; D007156:Immunologic Memory; D016023:Integrins / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D012401:Rotavirus / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D007072:Immunoglobulin D; D016023:Integrins; C071777:integrin alpha4beta7