The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells.
Control of the intracellular levels of phosphatidylinositol-(3, 4, 5)-trisphosphate by PI3K and phosphatase and tensin homolog (PTEN) is essential for B cell development and differentiation. Deletion of the PI3K catalytic subunit p110delta leads to a severe reduction in B1 and marginal zone (MZ) B cells, whereas deletion of PTEN results in their expansion. We have examined the relationship between these two molecules by generating mice with a B cell-specific deletion of PTEN (PTENB) and a concurrent germline deletion of p110delta. The expanded B1 cell population of PTENB mice was reduced to normal levels in PTENB/p110delta mutant mice, indicating a critical role for the p110delta isoform in the expansion of B1 cells. However, numbers of MZ B cells in the PTENB/p110delta mutants was intermediate between wild-type and PTENB-deficient mice, suggesting an additional role for other PI3K catalytic isoforms in MZ differentiation. Furthermore, the defective class switch recombination in PTENB B cells was only partially reversed in PTENB/p110delta double mutant B cells. These results demonstrate an epistatic relationship between p110delta and PTEN. In addition, they also suggest that additional PI3K catalytic subunits contribute to B cell development and function.
Janas
Michelle L
ML
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge, United Kingdom.
Hodson
Daniel
D
Stamataki
Zania
Z
Hill
Sue
S
Welch
Katie
K
Gambardella
Laure
L
Trotman
Lloyd C
LC
Pandolfi
Pier Paolo
PP
Vigorito
Elena
E
Turner
Martin
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D058534:Class I Phosphatidylinositol 3-Kinases; D017353:Gene Deletion; D017578:Immunoglobulin Class Switching; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011995:Recombination, Genetic; D019076:Transgenes
D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; C421683:Pik3cd protein, mouse; C487757:Pten protein, mouse