Connor Wilhelm completed the Pathology M.S. program by successfully defending his thesis on June 30th, 2023. He performed his thesis work in the laboratory of Dr. Nitin Karandikar, with additional mentorship from Dr. Alexander Boyden in the Karandikar group. Drs. Ashutosh Mangalam and Scott Lieberman also served on his thesis committee.

Connor’s thesis is entitled Proteolipid Protein-induced Mouse Model of Multiple Sclerosis Requires B Cell-mediated Antigen Presentation and represents an important novel contribution to the field of multiple sclerosis research. It identifies the required mechanism explaining B cell dependency in PLPECD-induced experimental autoimmune encephalomyelitis, a novel mouse model of MS developed by Dr. Boyden. This model provides a powerful system for focusing in vivo investigation of autoimmune demyelinating disease on critical pathogenic B cell:CD4 T cell interactions.

Importantly, Connor’s work was published on August 7, 2023 in the Journal of Immunology: https://doi.org/10.4049/jimmunol.2200721. The abstract for his publication can be seen below:

The pathogenic role B cells play in multiple sclerosis is underscored by the success of B cell depletion therapies. Yet, it remains unclear how B cells contribute to disease, although it is increasingly accepted that mechanisms beyond Ab production are involved. Better understanding of pathogenic interactions between B cells and autoreactive CD4 T cells will be critical for novel therapeutics. To focus the investigation on B cell:CD4 T cell interactions in vivo and in vitro, we previously developed a B cell–dependent, Ab-independent experimental autoimmune encephalomyelitis (EAE) mouse model driven by a peptide encompassing the extracellular domains of myelin proteolipid protein (PLPECD). In this study, we demonstrated that B cell depletion significantly inhibited PLPECD-induced EAE disease, blunted PLPECD-elicited delayed-type hypersensitivity reactions in vivo, and reduced CD4 T cell activation, proliferation, and proinflammatory cytokine production. Further, PLPECD-reactive CD4 T cells sourced from B cell–depleted donor mice failed to transfer EAE to naive recipients. Importantly, we identified B cell–mediated Ag presentation as the critical mechanism explaining B cell dependence in PLPECD-induced EAE, where bone marrow chimeric mice harboring a B cell–restricted MHC class II deficiency failed to develop EAE. B cells were ultimately observed to restimulate significantly higher Ag-specific proliferation from PLP178–191–reactive CD4 T cells compared with dendritic cells when provided PLPECD peptide in head-to-head cultures. We therefore conclude that PLPECD-induced EAE features a required pathogenic B cell–mediated Ag presentation function, providing for investigable B cell:CD4 T cell interactions in the context of autoimmune demyelinating disease.