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

Author

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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
    Laboratoire d’Hématologie, Centre Hospitalier Universitaire (CHU) Rennes)

  • Gersende Caron

    (UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
    Laboratoire d’Hématologie, Centre Hospitalier Universitaire (CHU) Rennes)

  • 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
    Laboratoire d’Immunologie, Thérapie Cellulaire et Hématopoïèse (ITeCH), Centre Hospitalier Universitaire (CHU) Rennes)

  • Thierry Fest

    (UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO
    Laboratoire d’Hématologie, Centre Hospitalier Universitaire (CHU) Rennes)

  • Céline Delaloy

    (UMR U1236, Université de Rennes 1, INSERM, Etablissement Français du Sang (EFS) de Bretagne, Equipe labellisée Ligue contre le Cancer, Labex IGO)

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.

Suggested Citation

  • Nicolas Hipp & Hannah Symington & Cédric Pastoret & Gersende Caron & Céline Monvoisin & Karin Tarte & Thierry Fest & Céline Delaloy, 2017. "IL-2 imprints human naive B cell fate towards plasma cell through ERK/ELK1-mediated BACH2 repression," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01475-7
    DOI: 10.1038/s41467-017-01475-7
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