Severe B cell deficiency in mice lacking the tec kinase family members Tec and Btk.
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.
Ellmeier
W
W
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine. wilfried.ellmeier@univie.ac.at
Jung
S
S
Sunshine
M J
MJ
Hatam
F
F
Xu
Y
Y
Baltimore
D
D
Mano
H
H
Littman
D R
DR
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
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