A regulatory role for Fcgamma receptors CD16 and CD32 in the development of murine B cells.

Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (FcgammaR) designated as FcgammaRII (CD32) and FcgammaRIII (CD16), but mature B lymphocytes only express FcgammaRII (CD32), which functions as an inhibitor of B-cell activation when it is induced to associate with mIgM. The functions of CD16 and CD32 on B-lineage precursor cells have not previously been investigated. To search for FcgammaR functions on developing B-lineage cells, normal murine bone marrow cells were cultured in the presence of 2.4G2, a rat monoclonal antibody that binds to CD16 and CD32, or in the presence of control normal rat IgG, and then the B-lineage compartment was analyzed for effects. Cultures that contained 2.4G2 showed enhanced growth and differentiation of B-lineage cells compared with control cultures. The enhancing effect of 2.4G2 also occurred when fluorescence-activated cell-sorted B-cell precursors (B220(+), sIgM-, HSAhigh, FcgammaR+) from normal bone marrow were cocultured with BMS2, a bone marrow stromal cell line, but not when they were cultured in BMS2-conditioned media. The enhancement of B-lineage development induced by 2.4G2 was CD16-dependent and CD32-dependent, because 2.4G2 did not effect B-lineage growth or differentiation in cultures of bone marrow from mice in which either the gene encoding CD16 or CD32 had been disrupted. Analysis of fresh bone marrow from the CD16 gene-disrupted mice showed normal numbers and distribution of cells within the B-cell compartment, but in CD32 gene-disrupted mice, the B-cell compartment was significantly enlarged. These experiments provide several lines of evidence that the FcgammaR expressed on murine B-cell precursors can influence their growth and differentiation.