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

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  • Arantxa Pérez-García

    (B Cell Biology Lab, Vascular Pathophysiology Area, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III
    Present address: Epigenetics of Cancer and Ageing Group, Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK)

  • 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)

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.

Suggested Citation

  • Arantxa Pérez-García & Ester Marina-Zárate & Ángel F. Álvarez-Prado & Jose M. Ligos & Niels Galjart & Almudena R. Ramiro, 2017. "CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16067
    DOI: 10.1038/ncomms16067
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