| http://purl.uniprot.org/citations/22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22422878 | http://www.w3.org/2000/01/rdf-schema#comment | "PI3Ks are key signaling enzymes required for triggering many immunological functions. In B lymphocytes, PI3K signaling is required for Ag-induced proliferation and robust production of most Ab isotypes. Paradoxically, PI3K was found to have a negatively regulatory function regarding Ab class switch recombination, and blockade of PI3K can strongly potentiate IgE switch. In this article, we explore the mechanisms of this unexpected negative regulatory function of PI3K regarding IgE. We demonstrate that p110δ PI3K selectively regulates IgE switch in a B cell-intrinsic manner by controlling germline transcription of the IgE promoter (εGLT). Although p110δ can regulate transcription of activation-induced cytidine deaminase via Akt, repression of εGLT and IgE switch is not dependent on Akt signaling. Inhibition of p110δ, but not Akt, leads to reduced expression of transcriptional repressor B cell lymphoma 6 (BCL6) and concomitant upregulation of εGLT and other BCL6-target genes. p110δ inhibitor treatment strikingly alters the balance between BCL6 and IRF4 (a transcription factor that antagonizes BCL6), leading to increased IRF4 and decreased BCL6 expression levels in germinal center B cells. Ectopic expression of BCL6 can partially overcome the elevated εGLTs and potentiated IgE switching in p110δ-inhibited B cells. To our knowledge, these results provide the first evidence that p110δ PI3K signaling regulates BCL6 expression and indicate that PI3K promotes the germinal center B cell program and selectively represses IgE switch by maintaining sufficient levels of BCL6."xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1103302"xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://purl.uniprot.org/core/author | "Zhang T.T."xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://purl.uniprot.org/core/author | "Marshall A.J."xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://purl.uniprot.org/core/author | "Makondo K.J."xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22422878 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://purl.uniprot.org/core/pages | "3700-3708"xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://purl.uniprot.org/core/title | "p110delta phosphoinositide 3-kinase represses IgE switch by potentiating BCL6 expression."xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://purl.uniprot.org/core/volume | "188"xsd:string |
| http://purl.uniprot.org/citations/22422878 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22422878 |
| http://purl.uniprot.org/citations/22422878 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22422878 |
| http://purl.uniprot.org/uniprot/#_A0A075B5P6-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_A0A075B6A0-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_A0A1W2P8F6-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_B0QZL5-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_B1AS24-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_B1AS25-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_B1AS26-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_B1AS27-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_B1AS28-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_O35904-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_Q24LN5-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |
| http://purl.uniprot.org/uniprot/#_P41183-mappedCitation-22422878 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22422878 |