IL-2 Imprints Human Naive B Cell Fate Towards Plasma Cell Through ERK/ELK1-mediated BACH2 Repression

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Nov 14

PMID 29129929

Citations 54

Authors

Nicolas Hipp

Hannah Symington

Cedric Pastoret

Gersende Caron

Celine Monvoisin

Karin Tarte

Thierry Fest

Celine Delaloy

Affiliations

Soon will be listed here.

Abstract

Plasma cell differentiation is a tightly regulated process that requires appropriate T cell helps to reach the induction threshold. To further understand mechanisms by which T cell inputs regulate B cell fate decision, we investigate the minimal IL-2 stimulation for triggering human plasma cell differentiation in vitro. Here we show that the timed repression of BACH2 through IL-2-mediated ERK/ELK1 signalling pathway directs plasma cell lineage commitment. Enforced BACH2 repression in activated B cells unlocks the plasma cell transcriptional program and induces their differentiation into immunoglobulin M-secreting cells. RNA-seq and ChIP-seq results further identify BACH2 target genes involved in this process. An active regulatory region within the BACH2 super-enhancer, under ELK1 control and differentially regulated upon B-cell activation and cellular divisions, helps integrate IL-2 signal. Our study thus provides insights into the temporal regulation of BACH2 and its targets for controlling the differentiation of human naive B cells.

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