VH1-46 is the dominant immunoglobulin heavy chain gene segment in rotavirus-specific memory B cells expressing the intestinal homing receptor α4β7

Memory B cells expressing the intestinal homing marker alpha(4)beta(7) 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 V-H and V-L repertoire in human IgD(-) B cells expressing the intestinal homing marker alpha(4)beta(7). 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 alpha(4)beta(7) 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-/alpha(4)beta(7)(+) 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-/alpha(4)beta(7)(+) B cells using the VH1-46 gene segment were not mutated, in contrast to systemic RV-specific IgD(-) B cells.