Reference

Nature Communications 8, Article number: 16067 (2017) doi:10.1038/ncomms16067 naturensp 420

Authors

Arantxa Pérez-García, Ester Marina-Zárate, Ángel F. Álvarez-Prado, Jose M. Ligos, Niels Galjart & Almudena R. Ramiro

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.

Description

En el estudio se analizó si el regulador transcripcional CTCF podía jugar un papel en el programa de diferenciación del centro germinal. Se encontró que en ausencia de CTCF, los ratones son incapaces de desarrollar centros germinales en respuesta a inmunización. En ensayos in vitro y mediante técnicas de secuenciación masiva de ARN, se ha descubierto que los linfocitos B deficientes en CTCF tienen su programa transcripcional profundamente alterado, de manera que muchos de los genes no se expresan como sería esperable en células de centro germinal, sino que por el contrario, se asemejan al de células plasmáticas. Por lo tanto, el estudio revela una función esencial de CTCF orquestando los cambios transcripcionales de la diferenciación terminal del linfocito B y contribuye a entender mejor los mecanismos que regulan la respuesta inmune.

 

 

foto de grupo 1

 

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo de investigación ‘Biología de los linfocitos B’ liderado por la Dra. Almudena Ramiro centra su estudio en los mecanismos reguladores y de diversificación que tienen lugar en los centros germinales durante una respuesta inmune, además de interesarse por los procesos linfomagénicos y autoinmunes asociados a los linfocitos B.

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