B-Cell-Specific MHCII Promotes Host-Microbiome Symbiosis

Author

Mary Melissa Roland

Date of Award

Spring 2023

Document Type

Open Access Dissertation

Department

Biomedical Science

First Advisor

Jason L. Kubinak

Abstract

Classical major histocompatibility complex class II (MHCII) molecules are cell surface glycoproteins that bind and present peptide antigens on the surface of antigen presenting cells (APCs). MHCII:peptide complexes engage T cell receptors (TCRs) and CD4 co-receptors thereby facilitating cognate interactions between CD4+ T cells and APCs, which is responsible for the development of antigen-specific reactions and long-lived immunity; so called TD antibody responses. This is a critical step in the host’s response to pathogens, commensals, environmental stimuli and tumors. IgA is the dominant antibody isotype secreted into the gut and it is thought that most of the IgA in the gut is produced by B cells that develop in a TiD manner. In this dissertation, we use a Rag1^-/- adoptive transfer model to show that B-cell-specific MHCII signaling crucial for the generation of GC-B and GC_TFH cells that can produce high-affinity, anti-commensal IgA responses generated against the gut microbiota, and B-cell-specific MHCII influences the gut-microbiome in an IgA-dependent manner. We then use a MHC^IIfl/flCD19^cre/+ mouse model to demonstrate that B-cell-specific MHCII signaling is an important factor minimizing the physiological cost of microbial colonization of the gut. We finally propose a common garden experiment in which B cells expressing one or two MHCII alleles are injected into B cell deficient mice to test the theory of the MHCII heterozygote advantage.

Rights

© 2023, Mary Melissa Roland

Recommended Citation

Roland, M. M.(2023). B-Cell-Specific MHCII Promotes Host-Microbiome Symbiosis. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/7192