To examine the molecular mechanism of B cell differentiation, we introduced rearranged immunoglobulin (Ig) mu- and kappa-chain genes into the NFS70 pro-B cell line and observed their maturation. The IgR(+)-transfectants had characteristics of mature surface IgM (sIgM)+ B220high CD40+ CD38+ CD25+ B cells. CD40 expression levels were regulated by stimulation via the IgR. In comparison to wild type NFS70 cells, NF-kappaB activity was up-regulated in the IgR transfectants. Anti-IgR crosslinking of IgR+ cells induced down-regulation of CD40 expression that correlated with down-regulation of NF-kappaB activity in the IgR(+)-transfectants. Immature CD19+ sIgD- B cells from bone marrow also showed an alteration of CD40 expression in response to anti-IgR crosslinking. The results suggest that expression of IgR on the surface is one of the factors responsible for further maturation of B cells.