Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/5106
CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation
Nat Commun. 2017; 8:16067
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.
3' REGULATORY REGION | C-MYC GENE | IGH LOCUS | T-CELLS | B-CELLS | CHROMATIN ARCHITECTURE | V(D)J RECOMBINATION | GENOME | EXPRESSION | BLIMP-1