Characterizing the Function of B Cells that Accumulate in the Inflamed Central Nervous System in Anti-Myelin Autoimmunity
Abstract
While the role of autoimmune T cells has been extensively studied in anti-myelin
autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ from other subsets, with the goal to identify potential pathogenic functions in a murine model of anti-myelin autoimmunity. Single-cell profiling of cells found in the CNS suggests that mature meningeal B cells upregulate interferon-induced genes and downregulate genes associated with MHC Class II molecules compared to naive follicular B cells. Characterizing the inflammatory and regulatory properties of individual B cell subsets will inform pathogenic B cell population targets in MS and other autoimmune diseases with similar B cell profiles.