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A constitutively active aryl hydrocarbon receptor causes loss of peritoneal B1 cells
Patrik Andersson1, Anna Ridderstad, Jacqueline McGuire
1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. patrik.andersson@imm.ki.se
Abstract:
The dioxin/aryl hydrocarbon (Ah) receptor functions as a ligand-activated transcription factor that mediates toxicity of dioxins and related environmental pollutants. We have developed a transgenic mouse model that expresses a constitutively active Ah receptor. The immune system is one of the most sensitive target organs for dioxin toxicity and we have therefore investigated alterations of different lymphocyte populations in these mice. The population of mature bone-marrow derived B cells was enlarged, consistent with previous findings in dioxin exposed mice. In contrast, the peritoneal population of CD5-expressing B cells (B1 cells) was significantly diminished. This is the first study that demonstrates the effect of an activated Ah receptor on B1 cells. Since these cells are important mediators of innate immunity against pathogens such as Influenza virus, these results may explain the decreased resistance against infections that has been documented after dioxin exposure.
Insights
A constitutively active aryl hydrocarbon (Ah) receptor enlarged B cells but diminished B1 cells, impacting innate immunity. This research explains reduced infection resistance following dioxin exposure.
Area of Science:
- Environmental toxicology
- Immunology
- Molecular biology
Background:
- The aryl hydrocarbon (Ah) receptor is a transcription factor mediating dioxin toxicity.
- The immune system is highly sensitive to dioxin exposure.
- Previous studies noted enlarged B cells in dioxin-exposed mice.
Purpose of the Study:
- To investigate the impact of a constitutively active Ah receptor on lymphocyte populations.
- To elucidate the role of Ah receptor signaling in B cell subset regulation.
- To understand the immunological basis for decreased infection resistance after dioxin exposure.
Main Methods:
- Development of a transgenic mouse model with a constitutively active Ah receptor.
- Analysis of lymphocyte populations, specifically B cell subsets (bone marrow and peritoneal).
- Comparison of findings with known effects of dioxin exposure.
Main Results:
- Enlargement of mature bone marrow-derived B cell populations observed.
- Significant reduction in peritoneal CD5-expressing B cells (B1 cells).
- This is the first study demonstrating Ah receptor activation's effect on B1 cells.
Conclusions:
- Constitutively active Ah receptor signaling alters B cell subset distribution.
- Diminished B1 cells may impair innate immune responses against pathogens like influenza.
- Findings provide a potential mechanism for increased susceptibility to infections post-dioxin exposure.