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...
| Autores: | , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/5106 |
| Acesso em linha: | http://hdl.handle.net/20.500.12105/5106 |
| Access Level: | acceso abierto |
| Palavra-chave: | 3' REGULATORY REGION C-MYC GENE IGH LOCUS T-CELLS B-CELLS CHROMATIN ARCHITECTURE V(D)J RECOMBINATION GENOME EXPRESSION BLIMP-1 |
| Resumo: | 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. |
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