VH1-46 is the dominant immunoglobulin heavy chain gene segment in rotavirus-specific memory B cells expressing the intestinal homing receptor alpha4beta7

• Published in: The Journal of immunology (1950) Vol. 174; no. 6; p. 3454
• Main Authors: Weitkamp, Jörn-Hendrik, Kallewaard, Nicole L, Bowen, Amber L, Lafleur, Bonnie J, Greenberg, Harry B, Crowe, Jr, James E
• Format: Journal Article
• Language: English
• Published: United States 15.03.2005
• Subjects: B-Lymphocytes - immunology; Blood Donors; Clone Cells; Genes, Immunoglobulin; Humans; Immunoglobulin D - metabolism; Immunologic Memory; Integrins - metabolism; Intestines - cytology; Intestines - immunology; Phenotype; Rotavirus - immunology; Somatic Hypermutation, Immunoglobulin
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.174.6.3454

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.