CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation
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.
|Persistent URL||dx.doi.org/10.1038/ncomms16067, hdl.handle.net/1765/108544|
Pérez-García, A. (Arantxa), Marina-Zárate, E. (Ester), Álvarez-Prado, Á.F. (Ángel F.), Ligos, J.M. (Jose M.), Galjart, N.J, & Ramiro, A.R. (Almudena R.). (2017). CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation. Nature Communications, 8. doi:10.1038/ncomms16067