Defining the Role of Unconventionally Activated Meningeal B Cells in CNS Autoimmune Inflammation

Background: With the development of new disease modifying therapies that target immune system cells called ‘B cells,’ it has become increasingly important to better understand the role of B cells in multiple sclerosis (MS). While we understand that B cells are important drivers of MS pathology, its mechanisms in the context of MS are not well understood.

Overview: A population of B cells accumulate in the meninges—the membranes that surround the brain and spinal cord—adjacent to demyelinating MS lesions usually in association with other immune cells, called T cells. Research suggests that B cells are activated through an unconventional pathway and that they may function to reactivate local autoimmune T cells to promote disease. Dr. Steven Kerfoot and team aims to characterize the pathogenic functions of meningeal B cells and will directly visualize their interactions with autoimmune T cells to understand the consequences of these interactions. This research will then target these interactions to test whether they can limit disease progression.

Impact: While drugs that destroy all B cells are effective in slowing the progression of MS, this is a very aggressive approach that eliminates an entire and very important branch of the immune system. Someone with MS could conceivably require treatment for decades, and the long-term consequences of B cell depletion are not known and potentially serious. By identifying the mechanism by which B cells promote MS progression we may be able to better target it, and to make therapies that are effective, but less potentially destructive.

Project Status: In Progress