Selection of antibody repertories: transfer of mature T lymphocytes modifies VH gene family usage in the actual and available B cell repertories of athymic mice

Abstract

The possible role of T lymphocytes in the selection of antibody repertories was investigated by comparing VH family usage in different B cell compartments of euthymic and athymic B6 mice. Analysis of VH gene family representation at the single cell level by in situ hybridization shows a diminished utilization of the VH J558 family in the effector compartment of the spleen and in small B cells of the lymph nodes of nude mice when compared to euthymic age-matched controls. Transfer of mature T cells from syngeneic donors increases expression of the VH J558 family in these two B cell compartments, not only abrogating the decreased utilization of the VH J558 family found in nude mice but further reinforcing the dominance of this family to levels of expression above those observed in euthymic controls. These changes are already evident by 5 days after T cell transfer and represent a permanent alteration of B cell repertoires as they persist for up to 1 year after T cell injection. Reconstitution of athymic mice with isolated T cell subsets induces different patterns of VH gene repertoires. Thus, while CD4+ cells enhance the expression of the VH J558 family, in CD8+ repopulated mice the utilization of the VH X-24 family increases in the splenic Ig-secreting cell pool. The present findings demonstrate that T lymphocytes modulate the selection of antibody repertoires in normal, non-immunized mice.