Modulation of B cell activation and effector function by the aryl hydrocarbon receptor in the rat
Suppression of the humoral immune response by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) occurs through activation of the aryl hydrocarbon receptor (AHR) and the B cell has been identified as one of the most sensitive targets to TCDD. Despite decades of studies in multiple species the exact mechanisms by which TCDD suppresses B cell activation and the primary IgM antibody response has yet to be elucidated. The magnitude of AHR regulation on B cell activation and effector function is also unknown. It was hypothesized that the targeted deletion of the AHR results in the loss of sensitivity of the B cell to suppression by TCDD and conversely in the augmentation of the primary IgM antibody response, which is mediated in part, through a greater magnitude in B cell activation in the absence of TCDD. The expression of surface markers CD80, CD86, and MHC II signify early activation events in the B cell and can be used to evaluate the magnitude of activation. Likewise, IgM secretion can be used to evaluate the magnitude in B cell effector function. Using a rat AHR knockout model, in vitro LPS activation of B cells resulted in higher expression of CD80, CD86 and MHC II in AHR knockout compared to wild type rats. Similarly, AHR knockout rats had an increased primary IgM antibody response with LPS activation. TCDD did not significantly alter CD80, CD86, and MHC II expression or the IgM antibody response of AHR knockout and wild type rats. This study has demonstrated that AHR is partly responsible for regulating the magnitude of B cell activation and effector function. -- Abstract.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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D'Ingillo, Shawna
- Thesis Advisors
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Kaminski, Norbert
- Committee Members
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Kaplan, Barbara
Ganey, Patricia
Copple, Bryan
- Date
- 2013
- Subjects
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Immune response
Immunology
Tetrachlorodibenzodioxin--Physiological effect
Tetrachlorodibenzodioxin--Toxicology
- Degree Level
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Masters
- Language
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English
- Pages
- xiii, 103 pages
- ISBN
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9781303601163
1303601168