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dc.contributor.authorDescatoire, Marc
dc.contributor.authorFritzen, Remi
dc.contributor.authorRotman, Samuel
dc.contributor.authorKuntzelman, Genevieve
dc.contributor.authorLeber, Xavier Charles
dc.contributor.authorDroz-Georget, Stephanie
dc.contributor.authorThrasher, Adrian J.
dc.contributor.authorTraggiai, Elisabetta
dc.contributor.authorCandotti, Fabio
dc.identifier.citationDescatoire , M , Fritzen , R , Rotman , S , Kuntzelman , G , Leber , X C , Droz-Georget , S , Thrasher , A J , Traggiai , E & Candotti , F 2022 , ' Critical role of WASp in germinal center tolerance through regulation of B cell apoptosis and diversification ' , Cell Reports , vol. 38 , no. 10 , 110474 .
dc.identifier.otherPURE: 278227820
dc.identifier.otherPURE UUID: 361ce6c1-352a-44b6-8470-d97b4372e0d4
dc.identifier.otherRIS: urn:68CA9669749374CB1A39CF20653F6917
dc.identifier.otherORCID: /0000-0003-3457-8364/work/109766815
dc.identifier.otherScopus: 85126171701
dc.identifier.otherWOS: 000768295500006
dc.descriptionThis project was supported by grant 310030-179251 from the Suisse National Science Foundation (SNF) (to F.C.), funds from the BLACKSWAN Foundation (BSF-005) (to M.D.), and the Wellcome Trust (to A.J.T.).en
dc.description.abstractA main feature of Wiskott-Aldrich syndrome (WAS) is increased susceptibility to autoimmunity. A key contribution of B cells to development of these complications has been demonstrated through studies of samples from affected individuals and mouse models of the disease, but the role of the WAS protein (WASp) in controlling peripheral tolerance has not been specifically explored. Here we show that B cell responses remain T cell dependent in constitutive WASp-deficient mice, whereas selective WASp deletion in germinal center B cells (GCBs) is sufficient to induce broad development of self-reactive antibodies and kidney pathology, pointing to loss of germinal center tolerance as a primary cause leading to autoimmunity. Mechanistically, we show that WASp is upregulated in GCBs and regulates apoptosis and plasma cell differentiation in the germinal center and that the somatic hypermutation-derived diversification is the basis of autoantibody development.
dc.relation.ispartofCell Reportsen
dc.rightsCopyright 2022 The Authors. This is an open access article under the CC BY-NC-ND license (
dc.subjectWiskott-Aldrich syndromeen
dc.subjectGerminal center B cellsen
dc.subjectQH301 Biologyen
dc.subjectQR180 Immunologyen
dc.titleCritical role of WASp in germinal center tolerance through regulation of B cell apoptosis and diversificationen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.description.statusPeer revieweden

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