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

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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Nature Communications, Nature Publishing Group, 2017, 8, pp.1443. 〈10.1038/s41467-017-01475-7〉
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01659591
Contributeur : Xavier Chard-Hutchinson <>
Soumis le : vendredi 8 décembre 2017 - 15:22:02
Dernière modification le : mercredi 16 mai 2018 - 11:24:11

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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, Nature Publishing Group, 2017, 8, pp.1443. 〈10.1038/s41467-017-01475-7〉. 〈hal-01659591〉

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