Date of Award

Spring 2021

Degree Type

Thesis

Department

Chemistry and Biochemistry

Director of Thesis

Dr. Jason L. Kubinak

First Reader

Mary M. Roland

Second Reader

Mary M. Roland

Abstract

Recent studies demonstrate that immunoglobulin A (IgA) is critical for limiting chronic inflammation, but the mechanism by which this occurs is undefined. Regulation of the composition of the commensal bacterial community in the gut (i.e. the microbiota) could be one mechanism. IgA can be produced through T-cell-dependent (TD) and T-cell-independent (TiD) pathways. While TiD IgA is the most abundant IgA secreted into the gut, the relative contribution of TD and TiD IgA in regulating microbiota composition is controversial. Antigen presentation by B cells to T cells is essential for TD responses, and this is carried out by MHC class II molecules. Here, we sought to address the hypothesis that B-cell-intrinsic MHCII antigen presentation promotes anti-commensal TD IgA responses that influence microbiota composition. In order to do this, RAG1-/- mice, that lack their own T and B cells, received adoptive transfers of wildtype (WT) T cells along with MHCII-positive (MHCII+) B cells, or WT T cells along with MHCII-deficient (MHCII-) B cells. Results of our experiments demonstrate that the presence of MHCII on B cells leads to higher levels of IgA secretion into the gut, is critical to the formation of germinal centers, enhances binding of gut bacteria by high-affinity IgA, and is associated with greater species richness in the gut microbial community. Our results support that TD IgA responses promote species diversity in the gut, which is thought to benefit host health.

First Page

1

Last Page

25

Rights

© 2021, Sergei Alexeev

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