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By using novel mouse models with a conditional deletion of the p110\u03b4 catalytic subunit of the PI3K pathway, we established that p110\u03b4 is required in T cells, but not in B cells, for the GC reaction. We found the formation of T follicular helper (TFH) cells to be critically dependent on p110\u03b4 in T cells. Furthermore, by deleting phosphatase and tensin homolog deleted on chromosome 10, which opposes p110\u03b4 in activated T cells, we found a positive correlation between increased numbers of TFH cells and GC B cells. These results are consistent with the hypothesis that T cell help is the limiting factor in the GC reaction. P110\u03b4 was not required for the expression of B cell lymphoma 6, the downregulation of CCR7, or T cell entry into primary follicles. Instead, p110\u03b4 was the critical catalytic subunit for ICOS downstream signaling and the production of key TFH cytokines and effector molecules. Our findings support a model in which the magnitude of the GC reaction is controlled by the activity of the PI3K pathway in TFH cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1001730","type":"journal-article","created":{"date-parts":[[2010,9,9]],"date-time":"2010-09-09T02:42:49Z","timestamp":1284000169000},"page":"4042-4052","source":"Crossref","is-referenced-by-count":204,"title":["Phosphoinositide 3-Kinase Activity in T Cells Regulates the Magnitude of the Germinal Center Reaction"],"prefix":"10.1093","volume":"185","author":[{"given":"Julia","family":"Rolf","sequence":"first","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Bell","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"Kovesdi","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L","family":"Janas","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalya R","family":"Soond","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise M C","family":"Webb","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Santinelli","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Saunders","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Hebeis","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Killeen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology , San Francisco, San Francisco, CA 94143"},{"name":"Department of Medicine, University of California , San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Okkenhaug","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Turner","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Signalling and Development, Babraham Institute , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,10,1]]},"reference":[{"key":"2025032411590314600_r1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1146\/annurev.iy.12.040194.001001","article-title":"Germinal centers","volume":"12","author":"MacLennan","year":"1994","journal-title":"Annu. 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