DEFECTS IN B-LYMPHOCYTE MATURATION AND T-LYMPHOCYTE ACTIVATION IN MICE LACKING JAK3

Biochemical studies of signaling mediated by many cytokine and growth factor receptors have implicated members of the Jak family of tyrosine kinases in these pathways. Specifically, Jak3 has been shown to be as sociated with the interleukin-2 (IL-2) receptor gamma chain, a compone nt of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Mice lackin g Jak3 showed a severe block in B cell development at the pre-B stage in the bone marrow. In contrast, although the thymuses of these mice w ere small, T cell maturation progressed relatively normally. In respon se to mitogenic signals, peripheral T cells in Jak3-deficient mice did not proliferate and secreted small amounts of IL-2. These data demons trate that Jak3 is critical for the progression of B cell development in the bone marrow and for the functional competence of mature T cells .