JAK3 ACTIVATION IN HUMAN LYMPHOCYTE PRECURSOR CELLS

Although expression of the Jak3 tyrosine kinase in T lymphocytes has b een thought to be restricted to mature, activated cells, mutations of Jak3 can lead to the development of a human severe combined immunodefi ciency (SCID) characterized by an absence of peripheral T lymphocytes. We therefore examined in detail the expression of Jak3 throughout hum an T cell differentiation and show that Jak3 is in fact present throug hout the entire developmental process, with high levels expressed in t hymocytes. Jak3 is highly expressed in double negative (CD4(-)CD8(-)) cells, one of the earliest stages of thymocyte differentiation, and ca n be activated via the IL-7 receptor. IL-7 is known to stimulate thymo cyte proliferation and initiate re-arrangement of the T cell receptor (TCR) beta gene, suggesting that the failure of mutated Jak3 proteins to transduce this signal may be responsible for failures in T cell dev elopment. While Jak3 SCID patients possess mature peripheral B cells, we demonstrate that the Jak3 tyrosine kinase is also expressed in huma n pre-B cells and can be activated by the pre-B cell growth factor IL- 7.