A REGULATORY ROLE FOR FC-GAMMA RECEPTORS CD16 AND CD32 IN THE DEVELOPMENT OF MURINE B-CELLS

Early in development, murine B-lineage progenitor cells express two cl asses of IgG Fc receptors (Fc gamma R) designated as Fc gamma RII (CD3 2) and Fc gamma RIII (CD16), but mature B lymphocytes only express Fc gamma RII (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 investigate d. To search for Fc gamma R functions on developing B-lineage cells, n ormal 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 pres ence of control normal rat IgG, and then the B-lineage compartment was analyzed for effects. Cultures that contained 2.4G2 showed enhanced g rowth and differentiation of B-lineage cells compared with control cul tures. The enhancing effect of 2.4G2 also occurred when fluorescence-a ctivated cell-sorted B-cell precursors (B220(+), sIgM(-), HSA(high), F c gamma R+) from normal bone marrow were cocultured with BMS2, a bone marrow stromal cell line, but not when they were cultured in BMS2-cond itioned media. The enhancement of B-lineage development induced by 2.4 G2 was CD16-dependent and CD32-dependent, because 2.4G2 did not effect B-lineage growth or differentiation in cultures of bone marrow from m ice in which either the gene encoding CD16 or CD32 had been disrupted. Analysis of fresh bone marrow from the CD16 gene-disrupted mice showe d normal numbers and distribution of cells within the B-cell compartme nt, but in CD32 gene-disrupted mice, the B-cell compartment was signif icantly enlarged. These experiments provide several lines of evidence that the Fc gamma R expressed on murine B-cell precursors can influenc e their growth and differentiation. (C) 1998 by The American Society o f Hematology.