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

Pérez-García, A., Marina-Zárate, E., Álvarez-Prado, Á. F., Ligos, J. M., Galjart, N. and Ramiro, A. R. (2017) CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation. Nature Communications, 8, 16067. (doi: 10.1038/ncomms16067) (PMID:28677680) (PMCID:PMC5504274)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Perez, Ms Arantxa
• Authors: Pérez-García, A., Marina-Zárate, E., Álvarez-Prado, Á. F., Ligos, J. M., Galjart, N., and Ramiro, A. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Nature Communications 8:16067
• Publisher Policy: Reproduced under a Creative Commons License