title: Aryl hydrocarbon receptor is required for optimal B-cell proliferation.
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.
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Matteo
authors.initials: M
authors.lastname: Villa
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Manolis
authors.initials: M
authors.lastname: Gialitakis
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Mauro
authors.initials: M
authors.lastname: Tolaini
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Ahlfors
authors.affiliation: Division of Cancer Research, University of Dundee Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Henderson
authors.affiliation: Division of Cancer Research, University of Dundee Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: C Roland
authors.initials: CR
authors.lastname: Wolf
authors.affiliation: Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Brink
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London, UK brigitta.stockinger@crick.ac.uk.
authors.forename: Brigitta
authors.identifier: 0000-0001-8781-336X
authors.initials: B
authors.lastname: Stockinger
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D049109:Cell Proliferation; D016213:Cyclins / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D020869:Gene Expression Profiling; D015847:Interleukin-4 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D016213:Cyclins; D011947:Receptors, Antigen, B-Cell; D018336:Receptors, Aryl Hydrocarbon; C539096:cyclin O, mouse; D015847:Interleukin-4; D019363:Cytochrome P-450 CYP1A1
keywords: B cells; aryl hydrocarbon receptor; cyclin O; proliferation