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

Nicolas Hipp, Hannah Symington, Cédric Pastoret, Gersende Caron, Céline Monvoisin, Karin Tarte, Thierry Fest () and Céline Delaloy ()
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Nicolas Hipp: UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
Hannah Symington: UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
Cédric Pastoret: UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
Gersende Caron: UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
Céline Monvoisin: UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
Karin Tarte: UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
Thierry Fest: UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
Céline Delaloy: UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01475-7

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