Pim-1 levels determine the size of early B lymphoid compartments in bone marrow

doi:10.1084/jem.178.5.1665

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Pim-1 levels determine the size of early B lymphoid compartments in bone marrow

J Domen, NM van der Lugt, D Acton, PW Laird, K Linders and A Berns
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.

The mouse proto-oncogene Pim-1, which encodes two cytoplasmic serine- threonine-specific protein kinases, is frequently activated by proviral insertion in murine leukemia virus-induced hematopoietic tumors. Transgenic mice overexpressing Pim-1 show a low incidence of spontaneous T cell lymphomas, whereas null mutant mice lack an obvious phenotype. We have analyzed the early B lymphoid compartment from both null mutant and E mu-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 impaired response in null mutant mice could be rescued by introduction of a functional Pim-1 transgene. Moreover, overexpression of Pim-1 facilitates the derivation of primitive lymphoid cell lines that are dependent on combined stimulation with IL- 7 and SF or insulin-like growth factor 1. These results for the first time identify the involvement of Pim-1 in a normal cellular function, as an important regulator of early B lymphopoiesis in mice.
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