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dc.contributor.authorAbdelrasoul, Henden
dc.contributor.authorWerner, Markusen
dc.contributor.authorSetz, Corinna Sen
dc.contributor.authorOkkenhaug, Klausen
dc.contributor.authorJumaa, Hassanen
dc.date.accessioned2018-04-05T15:50:27Z
dc.date.available2018-04-05T15:50:27Z
dc.date.issued2018-01-22en
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274601
dc.description.abstractAltmetric: 0More detail Article | OPEN PI3K induces B-cell development and regulates B cell identity Hend Abdelrasoul, Markus Werner, Corinna S. Setz, Klaus Okkenhaug & Hassan Jumaa Scientific Reports 8, Article number: 1327 (2018) doi:10.1038/s41598-018-19460-5 Download Citation Adaptive immunityB cells Received: 10 April 2017 Accepted: 02 January 2018 Published online: 22 January 2018 Abstract Phosphoinositide-3 kinase (PI3K) signaling is important for the survival of numerous cell types and class IA of PI3K is specifically required for the development of B cells but not for T cell development. Here, we show that class IA PI3K-mediated signals induce the expression of the transcription factor Pax5, which plays a central role in B cell commitment and differentiation by activating the expression of central B cell-specific signaling proteins such as SLP-65 and CD19. Defective class IA PI3K function leads to reduction in Pax5 expression and prevents B cell development beyond the stage expressing the precursor B cell receptor (pre-BCR). Investigating the mechanism of PI3K-induced Pax5 expression revealed that it involves a network of transcription factors including FoxO1 and Irf4 that directly binds to the Pax5 gene. Together, our results suggest that PI3K signaling links survival and differentiation of developing B cells with B cell identity and that decreased PI3K activity in pre-B cells results in reduced Pax5 expression and lineage plasticity.
dc.format.mediumElectronicen
dc.languageengen
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectB-Lymphocytesen
dc.subjectCells, Cultureden
dc.subjectCell Lineen
dc.subjectAnimalsen
dc.subjectMiceen
dc.subjectAdaptor Proteins, Signal Transducingen
dc.subjectAntigens, CD19en
dc.subjectLymphopoiesisen
dc.subjectCell Lineageen
dc.subjectInterferon Regulatory Factorsen
dc.subjectPhosphatidylinositol 3-Kinasesen
dc.subjectPAX5 Transcription Factoren
dc.subjectForkhead Box Protein O1en
dc.titlePI3K induces B-cell development and regulates B cell identity.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2018en
prism.publicationNameScientific reportsen
prism.startingPage1327
prism.volume8en
dc.identifier.doi10.17863/CAM.21741
dcterms.dateAccepted2018-01-02en
rioxxterms.versionofrecord10.1038/s41598-018-19460-5en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-01-22en
dc.contributor.orcidOkkenhaug, Klaus [0000-0002-9432-4051]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Reviewen


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International