title: Severe B cell deficiency in mice lacking the tec kinase family members Tec and Btk.
abstract: 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)M(lo)IgD(hi) B cells. Although Tec/Btk(null) 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.
authors: Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine. wilfried.ellmeier@univie.ac.at
authors: W
authors: W
authors: Ellmeier
authors: S
authors: S
authors: Jung
authors: M J
authors: MJ
authors: Sunshine
authors: F
authors: F
authors: Hatam
authors: Y
authors: Y
authors: Xu
authors: D
authors: D
authors: Baltimore
authors: H
authors: H
authors: Mano
authors: D R
authors: DR
authors: Littman
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D007072:Immunoglobulin D / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051917:Leukosialin; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D016296:Mutagenesis; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011995:Recombination, Genetic; D012795:Sialoglycoproteins / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D015703:Antigens, CD; D007070:Immunoglobulin A; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D051917:Leukosialin; D008070:Lipopolysaccharides; D008934:Mitogens; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; D017493:Leukocyte Common Antigens