Aryl hydrocarbon receptor is required for optimal B-cell proliferation

EMBO J. 2017 Jan 4;36(1):116-128. doi: 10.15252/embj.201695027. Epub 2016 Nov 14.

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.

Keywords: B cells; aryl hydrocarbon receptor; cyclin O; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / physiology*
  • Cell Proliferation*
  • Cyclins / metabolism
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Gene Expression Profiling
  • Interleukin-4 / metabolism
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Aryl Hydrocarbon / deficiency
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Transcription, Genetic

Substances

  • Cyclins
  • Receptors, Antigen, B-Cell
  • Receptors, Aryl Hydrocarbon
  • cyclin O, mouse
  • Interleukin-4
  • Cytochrome P-450 CYP1A1