Distinct pathways of B cell differentiation. I. Residual T cells in athymic mice support the development of splenic germinal centers and B cell memory without an induction of antibody.

B cell memory to T cell-dependent Ags develops in the germinal centers (GC). Here we report that thymus-deficient, nu/nu mice immunized with phosphorylcholine coupled to keyhole limpet hemocyanin (EPC-KLH) develop GC in the spleen in the absence of Ab-forming cell (AFC) response. However, the formation of GC on EPC-KLH immunization requires T cells, because 1) CB.1.7-scid mice reconstituted with B lymphocytes failed to develop GC without a supplement of CD4+ cells and 2) in vivo administration of an anti-CD4 mAb abolished the GC response in euthymic mice. Thus, it appears that the formation of GC in nu/nu mice was due to a low number of T cells that were detectable in situ within the splenic lymphoid follicles. The numbers of GC in individual Ag-stimulated nu/nu mice appeared to correlate with the density of T cells in the splenic sections. The B cells in these GC expressed T15, the dominant Id of anti-PC Ab, and became primed for an anamnestic response. Secondary challenge with EPC-KLH resulted in an increased number of GC without detectable AFC. However, when the Ag-primed nu/nu mice received CD4+ lymphocytes 1 day before the challenge, they demonstrated a vigorous AFC response that was predominantly IgM and significantly higher than the secondary response of nu/nu mice that had been reconstituted with CD4+ cells during both primary and secondary immunizations. Therefore, it appears that immunization of nu/nu mice may lead to an early step of B cell activation and memory development even though the T lymphocytes in these mice are incompetent to provide help for Ab formation. The memory and Ab pathways of B cell differentiation may involve different mechanisms of T cell help.