IL-2 imprints human naive B cell fate towards plasma cell through ERK/ELK1-mediated BACH2 repression - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2017

IL-2 imprints human naive B cell fate towards plasma cell through ERK/ELK1-mediated BACH2 repression

Résumé

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.

Domaines

Cancer

Dates et versions

hal-01659591 , version 1 (08-12-2017)

Identifiants

Citer

Nicolas Hipp, Hannah Symington, Cédric Pastoret, Gersende Caron, Céline Monvoisin, et al.. IL-2 imprints human naive B cell fate towards plasma cell through ERK/ELK1-mediated BACH2 repression. Nature Communications, 2017, 8 (1), pp.1443. ⟨10.1038/s41467-017-01475-7⟩. ⟨hal-01659591⟩
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