embj.201695027.pdf (884.34 kB)
Aryl hydrocarbon receptor is required for optimal B-cell proliferation
journal contributionposted on 2020-10-15, 16:10 authored by Matteo Villa, Manolis Gialitakis, Mauro Tolaini, Helena Ahlfors, Colin J Henderson, C Roland Wolf, Robert Brink, Brigitta Stockinger
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.
B cellsaryl hydrocarbon receptorcyclin OproliferationB-LymphocytesCell ProliferationCyclinsCytochrome P-450 CYP1A1Gene Expression ProfilingInterleukin-4Receptors, Antigen, B-CellReceptors, Aryl HydrocarbonTranscription, GeneticStockinger FC00115906 Biological Sciences08 Information and Computing Sciences11 Medical and Health SciencesDevelopmental Biology