PIM-1 LEVELS DETERMINE THE SIZE OF EARLY B-LYMPHOID COMPARTMENTS IN BONE-MARROW

The mouse proto-oncogene Pim-1, which encodes two cytoplasmic serine-t hreonine-specific protein kinases, is frequently activated by proviral insertion in murine leukemia virus-induced hematopoietic tumors. Tran sgenic mice overexpressing Pim-1 show a low incidence of spontaneous T cell lymphomas, whereas null mutant mice lack an obvious phenotype. W e have analyzed the early B lymphoid compartment from both null mutant and Emu-Pim-1 transgenic mice. The level of Pim-1 expression appears to be a determining factor in the ability of these cells to respond to the growth factors interleukin 7 (IL-7) and SF (steel factor). The im paired response in null mutant mice could be rescued by introduction o f a functional Pim-1 transgene. Moreover, overexpression of Pim-1 faci litates the derivation of primitive lymphoid cell lines that are depen dent on combined stimulation with IL-7 and SF or insulin-like growth f actor 1. These results for the first time identify the involvement of Pim-1 in a normal cellular function, as an important regulator of earl y B lymphopoiesis in mice.