Aryl hydrocarbon receptor is required for optimal B-cell proliferation

TY - JOUR

T1 - Aryl hydrocarbon receptor is required for optimal B-cell proliferation

AU - Villa, Matteo

AU - Gialitakis, Manolis

AU - Tolaini, Mauro

AU - Ahlfors, Helena

AU - Henderson, Colin J.

AU - Wolf, C. Roland

AU - Brink, Robert

AU - Stockinger, Brigitta

N1 - This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, The UK Medical Research Council and the Wellcome Trust. We would like to acknowledge the animal facility for expert management of breeding and maintenance of our mice as well as support by the Flow Cytometry facility and the Sequencing Facility. This work was funded by a Boehringer Ingelheim Fonds PhD Fellowship to M.V., a Wellcome Investigator Grant to B.S. and Cancer Research Programme Grant C4639/ A10822 to C.J.H. and C.R.W.

PY - 2017/1/4

Y1 - 2017/1/4

N2 - 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.

AB - 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.

U2 - 10.15252/embj.201695027

DO - 10.15252/embj.201695027

M3 - Article

C2 - 27875245

SN - 0261-4189

VL - 36

SP - 116

EP - 128

JO - EMBO Journal

JF - EMBO Journal

IS - 1

ER -