IL-3 increases production of B lymphoid progenitors from human CD34(+)CD38(-) cells

The effect of IL-3 on the B lymphoid potential of human hemopoietic stem ce lls is controversial. Murine studies suggest that B cell differentiation fr om uncommitted progenitors is completely prevented after short-term exposur e to IL-3, We studied B lymphopoiesis after IL-3 stimulation of uncommitted human CD34(+)CD38(-) cells, using the stromal cell line S17 to assay the B lymphoid potential of stimulated cells. In contrast to the murine studies, production of CD19(+) B cells from human CD31(+) CD38(-) cells was signifi cantly increased by a 3-day exposure to IL-3 (p < 0.001), IL-3, however, di d not increase B lymphopoiesis from more mature progenitors (CD34(+)CD38(+) cells) or from committed CD33(-)CD19(+) B cells, B cell production was inc reased whether CD34(-)CD38(-) cells were stimulated with IL-3 during cocult ivation on S17 stroma, on fibronectin, or in suspension. IL-3R<alpha> expre ssion was studied in CD34(+) populations by RT-PCR and FAGS. High IL-3R alp ha protein expression was largely restricted to myeloid progenitors. CD34()CD38(-) cells had low to undetectable levels of IL-3R alpha by FAGS. IL-3- responsive B lymphopoiesis was specifically found in CD34(+) cells with low or undetectable IL-3R alpha protein expression. IL-3 acted directly on pro genitor cells; single cell analysis showed that short-term exposure of CD34 (+)CD38(-) cells to IL-3 increased the subsequent cloning efficiency of B l ymphoid and B lymphomyeloid progenitors. We conclude that short-term exposu re to IL-3 significantly increases human B cell production by inducing prol iferation and/or maintaining the survival of primitive human progenitors wi th B lymphoid potential.