Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function - PubMed (original) (raw)

doi: 10.1038/ni892. Epub 2003 Feb 3.

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Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function

Amy N Anzelon et al. Nat Immunol. 2003 Mar.

Abstract

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.

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