DOI
https://doi.org/10.25772/P051-JX75
Defense Date
2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Microbiology & Immunology
First Advisor
Rebecca K. Martin
Abstract
Helminth infections are known to elicit a Th2 immune response that produces large quantities of IgE. Th2 immune responses are most well-known for causing allergic diseases. IgE is a key component to allergic disease. The relationship between helminth and allergies has for a long time been confounding. Helminth infections have been associated with a protective phenotype to allergic disease. B cells, the source of all antibody, come in two main types, B1 B cells and B2 B cells. B1 B cells are a fetal derived B cell that are known to be more innate like, and they produce natural antibodies. B2 B cells are BM derived and undergo affinity maturation to produce more effective antibody. Previous work from our lab showed that B1 B cells produce IgE that attenuated worm clearance and that B2 B cells cleared worm burden faster. However, these experiments utilized cell surface markers to sort B1 B cells from B2 B cells, and the BM can give rise to B1-like B cells. In these studies we utilize a mouse model that distinguishes B cells by their developmental lineage. We found that true B1 B cells do not make IgE in a helminth infection. BM derived B1-like B cells however significantly contribute to IgE production. Since the lineage of B cell that produced both clearing and protective IgE, we examined the follicular reaction in a helminth infection. Recently Tfh13s were described as a novel Tfh2 subtype that is critical for the production of allergen specific IgE. Mice infected with Nippostrongylus brasiliensis were found to have both classical Tfh2s as well as Tfh13s by day 10 post-infecton. The IgG and IgE producing cells followed the induction of Tfh2s and tfh13s. A memory response to Nippostrongylus brasiliensis was also examined for Tfhs. Tfh2s and Tfh13s appeared rapidly by day 4 post-infection. IgG1 and IgE producing cells also appeared by day 4. These data indicate that Tfh13s are in present in an immune response to Nippostrongylus brasiliensis, and that they have a role in both primary and memory responses.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-9-2025