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...

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Published in:Nature communications Vol. 8; no. 1; pp. 16067 - 12
Main Authors: Pérez-García, Arantxa, Marina-Zárate, Ester, Álvarez-Prado, Ángel F., Ligos, Jose M., Galjart, Niels, Ramiro, Almudena R.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 05.07.2017
Nature Publishing Group
Nature Portfolio
Subjects:
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Animals
B-Lymphocytes - physiology
CCCTC-Binding Factor - physiology
Cell activation
Cell Differentiation
Cell proliferation
Differentiation (biology)
Female
Genetic modification
Germinal Center - metabolism
Germinal centers
Humanities and Social Sciences
Immunoglobulins
Immunological memory
In vitro methods and tests
Lymphocytes B
Male
Memory cells
Mice
multidisciplinary
Plasma Cells
Positive Regulatory Domain I-Binding Factor 1 - metabolism
Primary Cell Culture
Restoration
Science
Science (multidisciplinary)
T cell receptors
Transcription
Transcription, Genetic
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Activated B cells differentiate into antibody-producing plasma cells in the germinal centre in secondary lymphoid organs. Here the authors show that this differentiation process and related transcription programs are modulated by the transcription factor CTCF, partly by suppressing the premature expression of Blimp-1.
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These authors contributed equally to this work.
Present address: Epigenetics of Cancer and Ageing Group, Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms16067