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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.


Journal article


J Immunol

Publication Date





739 - 746


Animals, B-Lymphocytes, Gene Deletion, Immunoglobulin Class Switching, Lymphocyte Activation, Mice, Mice, Mutant Strains, Mice, Transgenic, PTEN Phosphohydrolase, Phenotype, Phosphatidylinositol 3-Kinases, Phosphorylation, Protein Isoforms, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-bcl-2, Recombination, Genetic, Transgenes