Jak3 activation in human lymphocyte precursor cells

Although expression of the JAK3 tyrosine kinase in T lymphocytes has been thought to be restricted to mature, activated cells, mutations of JAK3 can lead to the development of a human severe combined immunodeficiency (SCID) characterized by an absence of peripheral T lymphocytes. We therefore examined in detail the expression of JAK3 throughout human T cell differentiation and show that JAK3 is in fact present throughout the entire developmental process, with high levels expressed in thymocytes. JAK3 is highly expressed in double negative (CD4- CD8-) cells, one of the earliest stages of thymocyte differentiation, and can be activated via the IL-7 Receptor. IL-7 is known to stimulate thymocyte 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 development. While JAK3 SCID patients possess mature peripheral B cells, we demonstrate that the JAK3 tyrosine kinase is also expressed in human pre-B cells and can be activated by the pre-B cell growth factor IL-7.