PMID- 12563260 OWN - NLM STAT- MEDLINE DCOM- 20030326 LR - 20221109 IS - 1529-2908 (Print) IS - 1529-2908 (Linking) VI - 4 IP - 3 DP - 2003 Mar TI - Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function. PG - 287-94 AB - 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. FAU - Anzelon, Amy N AU - Anzelon AN AD - Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, MC 0322, La Jolla, CA 92093, USA. FAU - Wu, Hong AU - Wu H FAU - Rickert, Robert C AU - Rickert RC LA - eng GR - AI41649/AI/NIAID NIH HHS/United States GR - GM07246/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030203 PL - United States TA - Nat Immunol JT - Nature immunology JID - 100941354 RN - 0 (Antigens, CD19) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Tumor Suppressor Proteins) RN - EC 3.1.3.2 (Phosphoric Monoester Hydrolases) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) SB - IM MH - Animals MH - Antigens, CD19/*metabolism MH - B-Lymphocytes/*metabolism MH - Cell Differentiation/physiology MH - Mice MH - PTEN Phosphohydrolase MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphoric Monoester Hydrolases/deficiency/*metabolism MH - Spleen/metabolism MH - Tumor Suppressor Proteins/deficiency/*metabolism EDAT- 2003/02/04 04:00 MHDA- 2003/03/27 05:00 CRDT- 2003/02/04 04:00 PHST- 2002/11/04 00:00 [received] PHST- 2003/01/13 00:00 [accepted] PHST- 2003/02/04 04:00 [pubmed] PHST- 2003/03/27 05:00 [medline] PHST- 2003/02/04 04:00 [entrez] AID - ni892 [pii] AID - 10.1038/ni892 [doi] PST - ppublish SO - Nat Immunol. 2003 Mar;4(3):287-94. doi: 10.1038/ni892. Epub 2003 Feb 3.