Aryl hydrocarbon receptor is required for optimal B-cell proliferation

Matteo Villa, Manolis Gialitakis, Mauro Tolaini, Helena Ahlfors, Colin J. Henderson, C. Roland Wolf, Robert Brink, Brigitta Stockinger (Lead / Corresponding author)

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    Abstract

    The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr(-/-)) B cells proliferate less than AhR-sufficient (Ahr(+/+)) cells following in vitro BCR stimulation and in vivo adoptive transfer models confirmed that Ahr(-/-) B cells are outcompeted by Ahr(+/+) cells. Transcriptome comparison of AhR-deficient and AhR-sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency.

    Original languageEnglish
    Pages (from-to)116-128
    Number of pages13
    JournalEMBO Journal
    Volume36
    Issue number1
    Early online date14 Nov 2016
    DOIs
    Publication statusPublished - 4 Jan 2017

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    Villa, M., Gialitakis, M., Tolaini, M., Ahlfors, H., Henderson, C. J., Wolf, C. R., Brink, R., & Stockinger, B. (2017). Aryl hydrocarbon receptor is required for optimal B-cell proliferation. EMBO Journal, 36(1), 116-128. https://doi.org/10.15252/embj.201695027