First Advisor

Gregory DeKrey

First Committee Member

Patrick Burns

Second Committee Member

Nicholas Pullen

Third Committee Member

Mark Thomas

Degree Name

Master of Science

Document Type

Thesis

Date Created

5-1-2024

Abstract

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α4β7. Both the AhR and CAMs are considered as potential therapeutic targets for diseases ranging from inflammatory disorders to autoimmune diseases.

To date, knowledge of AhR control of B cell development and expression of CAMs remains incomplete. Important factors such as state of B cell differentiation and sex have yet to be incorporated into studies on AhR regulation of CAMs. The aim of the current study was to examine how these factors might influence AhR mediated alterations in CCR9 and integrin α4β7 expression by B cells in vitro. Here, we report that B cells are sensitive to gut imprinting via the AhR only if AhR and immune activation occur within the first hour of a 24-hour period. Additionally, we observed that B cells derived from females displayed enhanced sensitivity to AhR mediated expression of gut associated migration markers compared to males. These results together suggest that the AhR exerts control over humoral responses in part through differential regulation of trafficking programs in distinct B cell subsets and in a sex-dependent manner.

Abstract Format

html

Disciplines

Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Digestive System Diseases | Immunity | Immunopathology | Immunoprophylaxis and Therapy | Molecular Genetics | Other Immunology and Infectious Disease | Pharmacology | Toxicology

Keywords

Aryl hydrocarbon receptor, B cell, mouse, mice, flow cytometry, in vitro, chemokine receptor 9, alpha4beta7, integrin, CCR, leukocyte trafficking, tissue homing, imprinting, immune activation, CH223191, C57BL/6, TCDD, sex

Language

English

Extent

98 pages

Rights Statement

Copyright is held by the author.

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