Date of Award
10-3-2023
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Microbiology and Immunology
First Advisor
Yee Ling Wu
Abstract
Immunoglobulin E (IgE) is the primary cause of allergic asthma. Allergen-specific IgE can be detected in the airway of allergic asthma patients even in the absence of circulating IgE, suggesting that IgE can be synthesized locally in the respiratory tract. However, the source of IgE-producing B cells, as well as how IgE responses arise and persist at mucosal sites are not fully understood. To address these questions, we modeled allergic asthma in mice by repeated intranasal administration of ragweed pollen and ovalbumin (OVA). We found that allergen exposure induced the production of local IgE in the airway and formation of aggregates of B and T lymphocytes near the airway epithelium that persisted for at least two months after allergen exposure. In secondary lymphoid tissues, B cells can participate in antigen-specific interactions with T cells producing the cytokine IL-4, which can induce B cells to undergo class switch recombination (CSR) to IgE. Using fluorescent reporter mice to track IgE-switching B cells, we found that the lungs were a major site of IgE CSR and identified IgG1+ memory B cells (MBCs) in the lungs as major IgE-switching cells. Using IL-4-GFP reporter mice, we found that IL-4-producing T cells were enriched in the lungs, and we demonstrated their ability to induce IgE CSR using an ex vivo culture system. Parabiosis experiments revealed that IgG1+ MBCs were resident in the lungs and mediate local IgE responses upon allergen rechallenge. Together, this study supports a model in which allergic lungs support lung-resident MBCs and IL-4-producing T cells that collaborate to promote local IgE production in the airway.
Recommended Citation
Nelson, Alexander James, "Lung Resident Memory B Cells Maintain Allergic IgE Responses in the Respiratory Tract" (2023). Dissertations. 4069.
https://ecommons.luc.edu/luc_diss/4069
