Inhibitory effect of interleukin 3 on early development of human B-lymphopoiesis

Interleukin 3 (IL-3) is known as a stimulator of proliferation and differentiation of non-lymphoid cells, but information about the activity of IL-3 in lymphopoiesis is limited. In the present study, we examined the effect of IL-3 on human B-lymphopoiesis using the co-culture system on a murine stromal cell line, MS-5, with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF). Although a large number of CD45(+)CD19(+) B cells were generated in the co-culture of cord blood CD34(+) cells, the addition of IL-3 to the co-culture suppressed the B-cell generation in a dose-dependent manner. In the co-culture, CD34(+)II-3 receptor a-chain (IL-3R alpha)(+) cells, but not IL3-Ra- cells, produced B cells, and IL-3 suppressed the B-cell generation from CD34(+)IL-3R alpha (+) cells, suggesting that IL-3 exerts an inhibitory effect through the binding to IL-3Ra on CD34(+) cells. Because the delayed addition of IL-3 and the short-term exposure to IL-3 showed that IL-3 acted as an inhibitor at an early stage of B-cell development from CD34(+) cells, before the generation of CD19(+) B cells, the effect of IL-3 on the early development of B cells from immature CD34(+)CD38(-) cells was examined. Individual colonies, produced from clone-sorted CD34(+)CD38(-) cells by SCF, thrombopoietin and a complex of IL-6/soluble IL-6R with or without IL-3, were divided into two fractions and analysed for B-cell potential using co-culture on MS-5 with SCF and G-CSF, and haematopoietic potential using methylcellulose clonal culture. Although some colonies cultured without IL-3 showed both B-cell and haematopoietic potential, all the colonies cultured with IL-3 showed only haematopoietic potential. These results indicate that IL-3 has an inhibitory effect on the B-cell generation from human lymphohaematopoietic progenitor cells.