Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function

Nat Immunol. 2003 Mar;4(3):287-94. doi: 10.1038/ni892. Epub 2003 Feb 3.


Phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) phosphatase serve essential functions in the regulation of cell growth, differentiation and survival by modulating intracellular phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) concentrations. Here we show that the conditional deletion of Pten in B cells led to the preferential generation of marginal zone (MZ) B cells and B1 cells. PTEN-deficient B cells were hyperproliferative in response to mitogenic stimuli, and exhibited a lower threshold for activation through the B cell antigen receptor. Inactivation of PTEN rescued germinal center, MZ B and B1 cell formation in CD19-/- mice, arguing that recruitment and activation of PI3K are the dominant roles for CD19 in these B cell subpopulations. These findings establish the central role of PI-3,4,5-P3 regulation in the differentiation of peripheral B cell subsets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD19 / metabolism*
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / physiology
  • Mice
  • PTEN Phosphohydrolase
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphoric Monoester Hydrolases / deficiency
  • Phosphoric Monoester Hydrolases / metabolism*
  • Spleen / metabolism
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / metabolism*


  • Antigens, CD19
  • Phosphoinositide-3 Kinase Inhibitors
  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase