CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation

Arantxa Pérez-García, Ester Marina-Zárate, Ángel F. Álvarez-Prado, Jose M. Ligos, Niels Galjart and Almudena R. Ramiro ()
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Arantxa Pérez-García: B Cell Biology Lab, Vascular Pathophysiology Area, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III
Ester Marina-Zárate: B Cell Biology Lab, Vascular Pathophysiology Area, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III
Ángel F. Álvarez-Prado: B Cell Biology Lab, Vascular Pathophysiology Area, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III
Jose M. Ligos: Cellomics Unit, Cell & Developmental Biology Area, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III
Niels Galjart: Erasmus Medical Center
Almudena R. Ramiro: B Cell Biology Lab, Vascular Pathophysiology Area, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms16067

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