Aryl hydrocarbon receptor is required for optimal B-cell proliferation

Area of Science:

• Immunology
• Molecular Biology
• Toxicology

Background:

• The aryl hydrocarbon receptor (AhR) is a transcription factor involved in xenobiotic metabolism.
• AhR is expressed in B cells, key players in adaptive immunity and targets of environmental pollutants.
• The physiological role of AhR in B cells remains largely undefined.

Purpose of the Study:

• To investigate the functional significance of the aryl hydrocarbon receptor (AhR) in B lymphocyte biology.
• To determine how AhR signaling impacts B cell activation, proliferation, and survival.

Main Methods:

• Examined AhR expression in B cells upon B-cell receptor (BCR) stimulation and IL-4 treatment.
• Utilized AhR ligands (e.g., FICZ) to assess pathway functionality, including nuclear translocation and target gene (Cyp1a1) induction.
• Compared proliferation and competitive fitness of AhR-deficient (Ahr-/-) and AhR-sufficient (Ahr+/+) B cells in vitro and in vivo.
• Conducted transcriptome analysis to identify AhR-regulated genes in B cells.

Main Results:

• AhR expression in B cells is upregulated by BCR engagement and IL-4.
• AhR signaling is functional in B cells, demonstrated by ligand-induced nuclear translocation and Cyp1a1 gene expression.
• AhR-deficient B cells exhibit reduced proliferation following BCR stimulation.
• In vivo adoptive transfer models show AhR-deficient B cells are outcompeted by AhR-sufficient counterparts.
• Cyclin O (Ccno), a direct AhR target gene, was identified as significantly affected by AhR deficiency.

Conclusions:

• The aryl hydrocarbon receptor (AhR) is functionally expressed in B cells and plays a significant role in their physiology.
• AhR signaling promotes B cell proliferation and competitive fitness, suggesting a role in immune responses.
• AhR-mediated regulation of genes like cyclin O (Ccno) is critical for B cell function.