title: MAPK p38 alpha is dispensable for lymphocyte development and proliferation.
abstract: Signals mediated by the p38alpha MAPK have been implicated in many processes required for the development and effector functions of innate and adaptive immune responses. As mice deficient in p38alpha exhibit embryonic lethality, most analyses of p38alpha 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 p38alpha(+/+), p38alpha(+/-), and p38alpha(-/-) embryonic stem (ES) cells through the intercrossing of p38alpha(+/-) 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 p38alpha(+/+), p38alpha(+/-), and p38alpha(-/-) ES cell lines. Moreover, proliferation of p38alpha(-/-) B and T cells in response to Ag receptor and non-Ag receptor stimuli was intact. Thus, p38alpha is not an essential component of signaling pathways required for robust B and T lymphocyte developmental, nor is p38alpha essential for the proliferation of mature B and T cells.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jeong M
authors.initials: JM
authors.lastname: Kim
authors.forename: J Michael
authors.initials: JM
authors.lastname: White
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
authors.forename: Barry P
authors.initials: BP
authors.lastname: Sleckman
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D003433:Crosses, Genetic; D004622:Embryo, Mammalian; D005260:Female; D005434:Flow Cytometry; D006580:Genetic Carrier Screening; D006720:Homozygote; D016130:Immunophenotyping; D007527:Isoenzymes / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000172:deficiency* / Q000502:physiology
chemical_list: D007527:Isoenzymes; D048051:p38 Mitogen-Activated Protein Kinases