Severe B cell deficiency in mice lacking the tec kinase family members Tec and Btk

J Exp Med. 2000 Dec 4;192(11):1611-24. doi: 10.1084/jem.192.11.1611.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Antigens, CD*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cell Division
  • Cell Line
  • Female
  • Immunoglobulin A / blood
  • Immunoglobulin D / biosynthesis
  • Immunoglobulin G / blood
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / blood
  • Leukocyte Common Antigens / biosynthesis
  • Leukosialin
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogens / pharmacology
  • Mutagenesis
  • Phenotype
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / physiology*
  • Recombination, Genetic
  • Sialoglycoproteins / biosynthesis
  • Spleen / cytology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD
  • Immunoglobulin A
  • Immunoglobulin D
  • Immunoglobulin G
  • Immunoglobulin M
  • Leukosialin
  • Lipopolysaccharides
  • Mitogens
  • Sialoglycoproteins
  • Spn protein, mouse
  • Tec protein-tyrosine kinase
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse
  • Leukocyte Common Antigens