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oai:repisalud.isciii.es:20.500.12105/51062024-10-31T11:41:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Perez-Garcia, Arantxa author Marina-Zarate, Ester author Alvarez-Prado, Angel Francisco author Ligos, Jose M. author Galjart, Niels author Ramiro, Almudena R author 2017 In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation. Nat Commun. 2017; 8:16067 2041-1723 http://hdl.handle.net/20.500.12105/5106 28677680 10.1038/ncomms16067 Nature Communications 3' REGULATORY REGION C-MYC GENE IGH LOCUS T-CELLS B-CELLS CHROMATIN ARCHITECTURE V(D)J RECOMBINATION GENOME EXPRESSION BLIMP-1 CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation