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The Journal of Immunology, 2005, 174: 1239-1244.
Copyright © 2005 by The American Association of Immunologists

MAPK p38{alpha} Is Dispensable for Lymphocyte Development and Proliferation1

Jeong M. Kim, J. Michael White, Andrey S. Shaw and Barry P. Sleckman2

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

Signals mediated by the p38{alpha} MAPK have been implicated in many processes required for the development and effector functions of innate and adaptive immune responses. As mice deficient in p38{alpha} exhibit embryonic lethality, most analyses of p38{alpha} function in lymphocytes have relied on the use of pharmacologic inhibitors and dominant-negative or constitutively active transgenes. In this study, we have generated a panel of low passage p38{alpha}+/+, p38{alpha}+/–, and p38{alpha}–/– embryonic stem (ES) cells through the intercrossing of p38{alpha}+/– mice. These ES cells were used to generate chimeric mice by RAG-deficient blastocyst complementation, with the lymphocytes in these mice being derived entirely from the ES cells. Surprisingly, B and T cell development were indistinguishable when comparing chimeric mice generated with p38{alpha}+/+, p38{alpha}+/–, and p38{alpha}–/– ES cell lines. Moreover, proliferation of p38{alpha}–/– B and T cells in response to Ag receptor and non-Ag receptor stimuli was intact. Thus, p38{alpha} is not an essential component of signaling pathways required for robust B and T lymphocyte developmental, nor is p38{alpha} essential for the proliferation of mature B and T cells.




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