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.
Sharfe
N
N
Department of Pediatrics, University of Toronto and the Hospital for Sick Children, Canada.
Dadi
H K
HK
O'Shea
J J
JJ
Roifman
C M
CM
D001402:B-Lymphocytes / Q000201:enzymology; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D053616:Janus Kinase 3; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016511:Severe Combined Immunodeficiency / Q000209:etiology; D013601:T-Lymphocytes / Q000201:enzymology*
D015851:Interleukin-7; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3