Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Steven M. Kerfoot

Abstract

The clinical success of B cell-depleting therapies in multiple sclerosis (MS) has identified an important, yet poorly understood pathogenic role for B cells in disease. An animal model of MS, experimental autoimmune encephalomyelitis (EAE), is typically induced through immunization with short myelin-derived peptides. B cells recognize whole proteins and not peptides, therefore their activation and involvement in peptide models of EAE is largely excluded. The goal of this study was to develop a novel fusion myelin protein reagent (MOGtag) to induce autoimmune responses in mice that incorporate T and B cell recognition of antigen. Characterization of the autoimmune response revealed the formation of a T cell-dependent germinal center B cell response. Further, immunization with MOGtag resulted in a chronic disease with evidence of an ongoing immune response, and central nervous system pathology featuring T cell infiltration of white and gray matter as well as formation of meningeal B cell clusters.

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