Jak3 activation in human lymphocyte precursor cells

Clinical and Experimental Immunology
N SharfeC M Roifman

Abstract

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.

Citations

May 23, 1998·Annual Review of Immunology·W J Leonard, J J O'Shea
Jan 29, 2014·JAK-STAT·Pramod DarvinYoung Mok Yang
Nov 13, 2010·Expert Review of Anticancer Therapy·Fatih M UckunSanjive Qazi
Jul 4, 1998·The Journal of Biological Chemistry·P A GoodmanF M Uckun
Mar 5, 2003·Leukemia & Lymphoma·Carla M WoodFaith M Uckun
Apr 17, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tatsiana AudzevichRolf Jessberger
Oct 26, 2020·Molecular Biology Reports·Eliana Rita SanpaoloFrancesco Paolo Cantatore

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