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

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 diff...

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Bibliographic Details
Published in:Nature communications 2017-11, Vol.8 (1), p.1443-17, Article 1443
Main Authors: Hipp, Nicolas, Symington, Hannah, Pastoret, Cédric, Caron, Gersende, Monvoisin, Céline, Tarte, Karin, Fest, Thierry, Delaloy, Céline
Format: Article
Language:English
Subjects:
631/250/127/1213
631/250/1619/40/1742
631/250/2152/2498
631/250/2502
Active control
Blood plasma
Cancer
Cell activation
Cell differentiation
Cell fate
Cell lineage
Differentiation (biology)
Extracellular signal-regulated kinase
Humanities and Social Sciences
Immunoglobulin M
Interleukin 2
Life Sciences
Lymphocyte receptors
Lymphocytes B
Lymphocytes T
multidisciplinary
Plasma
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Signal transduction
Signaling
Target recognition
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Summary: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. T cells help B cells to differentiate into antibody-producing plasma cells. Here the authors show that T cells produce interleukin-2 to activate ERK/ELK1 and suppress BACH2 expression by modulating the BACH2 super-enhancer, thereby altering BACH2 downstream transcription programs for plasma cell differentiation.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-01475-7