Date of Award

6-3-2025

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

First Advisor

Yee Ling Wu

Second Advisor

Dorothy Sojka; Phong Le

Abstract

Exposure to microbial products has been demonstrated to be inversely correlated to allergic conditions. Toll- like receptors sense microbial products and modulate immune responses. Our lab previously found that Toll-like receptor 9 signaling activated with microbial DNA mimicry reduced IgE production by decreasing germline transcription at the I-epsilon locus, a prerequisite for class switching. In this study, we investigate the direct effects and the mechanisms of activating other TLRs expressed on B cells on decreasing IgE class switching in vitro. To monitor class switching to IgE in mouse B cells, we use a reporter mouse strain that tracks I-epsilon germline transcription by the expression of a fluorescent protein. We stimulate mouse splenic B cells with anti-CD40 antibodies and IL-4 to drive class switching to IgE, and measure whether the addition of different TLR agonists reduces germline transcription. Additionally, we measure the expression of CD40 and IL-4 receptor on cultured cells to test if TLR agonists decrease cell responsiveness to these signals needed for class switching. We also investigate other mechanisms that may lead to decreased IgE production including plasma cell differentiation. Lastly, we adapt an in vitro human tonsil organoid system, stimulate the tonsil organoid with model protein antigens to induce antigen specific antibody responses. We aim to use this system to study the production of IgE as well as to test the effect of modulating TLR signaling in B cells on IgE response.

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Available for download on Thursday, August 19, 2027

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Microbiology Commons

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