Reduced formation of phosphatidic acid upon B-cell receptor triggering of mouse B-lymphocytes lacking Bruton's tyrosine kinase

Scand J Immunol. 2000 Jul;52(1):30-8. doi: 10.1046/j.1365-3083.2000.00747.x.


Btk deficient (BtkM) mouse B-lymphocytes do not proliferate when stimulated with anti-immunoglobulin (anti-Ig) antibodies. In order to characterize the molecular basis of this unresponsiveness we have compared early signal transduction pathways triggered by ligating the B cell antigen receptor (BCR) of purified resting B cells from normal C57BL/6 (wild-type) and BtkM mice on C57BL/6 background. BCR-induced signalling events that occur during the first few minutes of activation, such as bulk tyrosine phosphorylations, mitogen-activated protein kinase (MAPK) activation, PI3-kinase dependent PKB/Akt kinase phosphorylation/activation and PLCgamma2 tyrosine phosphorylation are comparable in wild type and BtkM B cells. However, the initial extracellular calcium influx is reduced and the BCR-induced accumulation of phosphatidic acid (PA) display a more transient profile in the BtkM cells. BCR ligation did not induce detectable phosphatidyl-choline PLD activity, suggesting that the reduced PA is owing to a reduction in the phospho-inositide hydrolysis. These findings further support the notion that the proliferative defect of Btk deficient mouse B cells in response to anti-immunoglobulin stimulation stems from a failure to sustain phospholipase-dependent signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • B-Lymphocytes / metabolism
  • Calcium / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidic Acids / biosynthesis*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphorylation
  • Protein-Tyrosine Kinases / physiology*
  • Receptors, Antigen, B-Cell / physiology*
  • Receptors, IgG / physiology
  • Species Specificity
  • Tyrosine / metabolism


  • Phosphatidic Acids
  • Receptors, Antigen, B-Cell
  • Receptors, IgG
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse
  • Mitogen-Activated Protein Kinases
  • Calcium