Aryl hydrocarbon receptor is required for optimal B-cell proliferation.
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.
|Authors||Villa, M.; Gialitakis, M.; Tolaini, M1.; Ahlfors, H.; Henderson, CJ.; Wolf, CR.; Brink, R.; Stockinger, B.|
|Publisher Name||EMBO JOURNAL|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/27875245|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/14017|