title: B-cell responses to B-cell activation factor of the TNF family (BAFF) are impaired in the absence of PI3K delta.
abstract: B-cell activating factor of the TNF family (BAFF) is critical for the survival and maturation of B cells. The molecular mechanisms by which BAFF regulates the survival of developing B cells are becoming better understood. Recent evidence has begun to emerge demonstrating a role for the PI3K/Akt signalling pathway in response to BAFF. However, the importance of the PI3K family for BAFF-signalling and the effects of loss of PI3K function on BAFF responses are still unknown. We therefore investigated the BAFF-mediated responses of B cells deficient for the PI3K catalytic subunit P110delta. We find that the loss of P110delta impairs the BAFF-mediated survival of cultured B cells demonstrating a direct role for this member of the PI3K family in regulating the survival of B cells in response to BAFF. P110delta was required for the growth of B cells in response to BAFF and was critical for the upregulation of the receptor for BAFF following BCR crosslinking. Our findings reveal an important role for p110delta in regulating B-cell responses to BAFF.
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK. tom.henley@bbsrc.ac.uk
authors.forename: Thomas
authors.initials: T
authors.lastname: Henley
authors.forename: Dorottya
authors.initials: D
authors.lastname: Kovesdi
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D058534:Class I Phosphatidylinositol 3-Kinases; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D053264:B-Cell Activating Factor; D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; C421683:Pik3cd protein, mouse