Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function.
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.
Anzelon
Amy N
AN
Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, MC 0322, La Jolla, CA 92093, USA.
Wu
Hong
H
Rickert
Robert C
RC
D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D051379:Mice; D051059:PTEN Phosphohydrolase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000378:metabolism*
D018941:Antigens, CD19; D000081082:Phosphoinositide-3 Kinase Inhibitors; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase