Ellmeier, Wilfried and Jung, Steffen and Sunshine, Mary Jean and Hatam, Farah and Xu, Yang and Baltimore, David and Mano, Hiroyuki and Littman, Dan R. (2000) Severe B Cell Deficiency in Mice Lacking the Tec Kinase Family Members Tec and Btk. Journal of Experimental Medicine, 192 (11). pp. 1611-1623. ISSN 0022-1007. PMCID PMC2193106. http://resolver.caltech.edu/CaltechAUTHORS:ELLjem00
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The cytoplasmic protein tyrosine kinase Tec has been proposed to have important functions in hematopoiesis and lymphocyte signal transduction. Here we show that Tec-deficient mice developed normally and had no major phenotypic alterations of the immune system. To reveal potential compensatory roles of other Tec kinases such as Bruton's tyrosine kinase (Btk), Tec/Btk double-deficient mice were generated. These mice exhibited a block at the B220+CD43+ stage of B cell development and displayed a severe reduction of peripheral B cell numbers, particularly immunoglobulin (Ig)MloIgDhi B cells. Although Tec/Btknull mice were able to form germinal centers, the response to T cell–dependent antigens was impaired. Thus, Tec and Btk together have an important role both during B cell development and in the generation and/or function of the peripheral B cell pool. The ability of Tec to compensate for Btk may also explain phenotypic differences in X-linked immunodeficiency (xid) mice compared with human X-linked agammaglobulinemia (XLA) patients.
|Additional Information:||©2000 The Rockefeller University Press. RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode. Submitted: 12 October 2000. Accepted: 19 October 2000. We thank Naomi Rosenberg for the A-MuLV producer cell line, Owen Witte for providing a Btk-cDNA probe, Derya Unutmaz for initial help with proliferation assays, William O'Brien for genotyping, and Yongrui Zou and Thomas Winkler for their critical reading of the manuscript. W. Ellmeier was initially supported by an Erwin-Schrödinger-Fellowship from the Austrian Science Fund and then by the Howard Hughes Medical Institute. Currently, W. Ellmeier is an Austrian Program for Advanced Research and Technology (APART) Fellow of the Austrian Academy of Science. S. Jung is supported by a Leukemia Society Fellowship. W. Ellmeier was an Associate and D.R. Littman is an Investigator of the Howard Hughes Medical Institute.|
|Subject Keywords:||gene targeting; B cell development; lymphocytes; signaling; X-linked immunodeficiency|
|PubMed Central ID:||PMC2193106|
|Usage Policy:||RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.|
|Deposited By:||Archive Administrator|
|Deposited On:||21 Jul 2008 23:38|
|Last Modified:||11 Apr 2017 17:11|
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