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Deletion of the PI3K catalytic subunit p110\u03b4 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 p110\u03b4. The expanded B1 cell population of PTENB mice was reduced to normal levels in PTENB\/p110\u03b4 mutant mice, indicating a critical role for the p110\u03b4 isoform in the expansion of B1 cells. However, numbers of MZ B cells in the PTENB\/p110\u03b4 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\/p110\u03b4 double mutant B cells. These results demonstrate an epistatic relationship between p110\u03b4 and PTEN. In addition, they also suggest that additional PI3K catalytic subunits contribute to B cell development and function.<\/jats:p>","DOI":"10.4049\/jimmunol.180.2.739","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:09:13Z","timestamp":1397862553000},"page":"739-746","source":"Crossref","is-referenced-by-count":34,"title":["The Effect of Deleting p110\u03b4 on the Phenotype and Function of PTEN-Deficient B Cells"],"prefix":"10.1093","volume":"180","author":[{"given":"Michelle L","family":"Janas","sequence":"first","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, The Babraham Institute , Babraham, Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hodson","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, The Babraham Institute , Babraham, Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zania","family":"Stamataki","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, The Babraham Institute , Babraham, Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Hill","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, The Babraham Institute , Babraham, Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Welch","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, The Babraham Institute , Babraham, Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, The Babraham Institute , Babraham, Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd C","family":"Trotman","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor , NY 11724"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo","family":"Pandolfi","sequence":"additional","affiliation":[{"name":"Cancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vigorito","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, The Babraham Institute , Babraham, Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Turner","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, The Babraham Institute , Babraham, Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,1,15]]},"reference":[{"key":"2025032610015913800_R1","first-page":"1897","volume-title":"J. 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