Aryl hydrocarbon receptor is required for optimal B‐cell proliferation

• Matteo Villa ^[1] ; Manolis Gialitakis ^[1] ; Mauro Tolaini ^[1] ; Helena Ahlfors ^[1] ; Colin J Henderson ^[2] ; C Roland Wolf ^[2] ; Robert Brink ^[3] ; Brigitta Stockinger ^[1]
  1. [1] Francis Crick Institute

     Francis Crick Institute

     Reino Unido

     
  2. [2] University of Dundee

     University of Dundee

     Reino Unido

     
  3. [3] Garvan Institute of Medical Research

     Garvan Institute of Medical Research

     Australia

     

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 1, 2017, págs. 116-128
• Idioma: inglés
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• Resumen

  • 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.