BIDIRECTIONAL EFFECT OF INTERLEUKIN-10 ON EARLY MURINE B-CELL DEVELOPMENT - STIMULATION OF FLT3-LIGAND PLUS INTERLEUKIN-7-DEPENDENT GENERATION OF CD19(-) PROB CELLS FROM UNCOMMITTED BONE-MARROW PROGENITOR CELLS AND GROWTH-INHIBITION OF CD19(+) PROB CELLS

B-cell commitment and early development from multipotent hematopoietic progenitor cells has until recently been considered to be dependent o n direct interaction with stromal cells. We recently showed that the f lt3 ligand (FL) has a unique ability to interact with interleukin-7 (I L-7) to directly and selectively promote B-cell development from murin e bone marrow progenitor cells with a combined myeloid and lymphoid po tential. Here we report that whereas IL-10 alone has no ability to sti mulate growth of primitive (Lin(-)Sca-1(+)c-kit(+)) bone marrow progen itor cells, it potently enhances FL + IL-7-induced proliferation (seve nfold). This enhanced proliferation results from recruitment of progen itors unresponsive to FL + IL-7 alone, as well as from increased growt h of individual clones, resulting in a 7,000-fold cellular expansion o ver 12 days. Single cell cultures and delayed addition studies suggest ed that the stimulatory effect of IL-10 was directly mediated on the p rogenitor cells. The cells generated in response to FL + IL-7 + IL-10 appeared to be almost exclusively proB cells, as shown by their expres sion of B220, CD24, CD43, and lack of expression of cp, myeloid, eryth roid, and T-cell surface antigens. Although IL-10 also enhanced kit li gand (KL) + IL-7-induced proliferation of Lin(-)Sca-1(+)c-kit(+).