Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/100438
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dc.contributor.authorSu, I-hsinen
dc.contributor.authorTalukder, Asoke K.en
dc.contributor.authorNojima, Takuyaen
dc.contributor.authorDoglioni, Claudioen
dc.contributor.authorKitamura, Daisukeen
dc.contributor.authorToellner, Kai-Men
dc.contributor.authorCasola, Stefanoen
dc.contributor.authorCaganova, Marietaen
dc.contributor.authorCarrisi, Chiaraen
dc.contributor.authorVarano, Gabrieleen
dc.contributor.authorMainoldi, Federicaen
dc.contributor.authorZanardi, Federicaen
dc.contributor.authorGermain, Pierre-Lucen
dc.contributor.authorGeorge, Lauraen
dc.contributor.authorAlberghini, Federicaen
dc.contributor.authorFerrarini, Lucaen
dc.contributor.authorPonzoni, Maurilioen
dc.contributor.authorTesta, Giuseppeen
dc.date.accessioned2013-11-29T00:48:26Zen
dc.date.accessioned2019-12-06T20:22:38Z-
dc.date.available2013-11-29T00:48:26Zen
dc.date.available2019-12-06T20:22:38Z-
dc.date.copyright2013en
dc.date.issued2013en
dc.identifier.citationCaganova, M., Carrisi, C., Varano, G., Mainoldi, F., Zanardi, F., Germain, P. L., et al. (2013). Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis. Journal of Clinical Investigation, 1-14.en
dc.identifier.issn0021-9738en
dc.identifier.urihttps://hdl.handle.net/10356/100438-
dc.identifier.urihttp://hdl.handle.net/10220/17889en
dc.description.abstractProtection against deadly pathogens requires the production of high-affinity antibodies by B cells, which are generated in germinal centers (GCs). Alteration of the GC developmental program is common in many B cell malignancies. Identification of regulators of the GC response is crucial to develop targeted therapies for GC B cell dysfunctions, including lymphomas. The histone H3 lysine 27 methyltransferase enhancer of zeste homolog 2 (EZH2) is highly expressed in GC B cells and is often constitutively activated in GC-derived non-Hodgkin lymphomas (NHLs). The function of EZH2 in GC B cells remains largely unknown. Herein, we show that Ezh2 inactivation in mouse GC B cells caused profound impairment of GC responses, memory B cell formation, and humoral immunity. EZH2 protected GC B cells against activation-induced cytidine deaminase (AID) mutagenesis, facilitated cell cycle progression, and silenced plasma cell determinant and tumor suppressor B-lymphocyte–induced maturation protein 1 (BLIMP1). EZH2 inhibition in NHL cells induced BLIMP1, which impaired tumor growth. In conclusion, EZH2 sustains AID function and prevents terminal differentiation of GC B cells, which allows antibody diversification and affinity maturation. Dysregulation of the GC reaction by constitutively active EZH2 facilitates lymphomagenesis and identifies EZH2 as a possible therapeutic target in NHL and other GC-derived B cell diseases.en
dc.format.extent14 p.en
dc.language.isoenen
dc.relation.ispartofseriesJournal of clinical investigationen
dc.rights© 2013 The American Society for Clinical Investigation. This paper was published in Journal of Clinical Investigation and is made available as an electronic reprint (preprint) with permission of The American Society for Clinical Investigation. The paper can be found at the following official DOI: [http://dx.doi.org/10.1172/JCI70626].  One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.en
dc.subjectDRNTU::Science::Biological sciences::Molecular biologyen
dc.titleGerminal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesisen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.identifier.doi10.1172/JCI70626en
dc.description.versionPublished versionen
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