Multiple Sclerosis Society of Canada

The Role of Antibody-Secreting Cells in MS/EAE

Principal Investigator: Dr. Jennifer Gommerman

Affiliation: University of Toronto

Year awarded: 2018-2019

Amount Awarded: $370,500

Keywords: B cells, plasma cells, gut microbiome

Summary:

  • B cells have a dual role in multiple sclerosis (MS). A subset of B cells slow the disease course in MS while another subset have detrimental effects on MS.
  • The gut microbiome is the richest source of B cells. The role of a subset of B cells, called plasma cells, found in the gut microbiome is unknown.
  • The research team will:
    • Determine the function, localization, and cellular and molecular interactors of plasma cells in animal model of MS-like disease.

Project Description:

B cell depletion therapy using rituximab/ocrelizumab results in substantial reductions in new MS relapses. B cells have a dual role: a subset of B cell is shown to slow disease progression whereas another subset have been shown to have detrimental effects on MS. The question remains how B cells contribute to MS disease. One of the key factors that may play a role in shaping B cell behaviour is the gut environment. In fact, the gut is the richest source of B cells in the body. An important cellular byproduct of B cells in the gut is antibody-producing plasma cells. Whether plasma cells play a role in the success or failure of B cell modifying therapies remains untested. Dr. Jennifer Gommerman’s project will examine if plasma cells derived from the gut environment directly or indirectly attenuate MS symptoms. To do so, the research team will determine the cellular targets of plasma cells in an animal model of MS, identify the migration and localization of plasma cells and pinpoint how plasma cells regulate MS in an animal model. The ultimate goal of the project is to identify the mechanisms through which some B cells ameliorates MS while others worsen the disease. If successful, the team will employ this knowledge to the rational design of better treatments for MS.

Potential Impact: Better understand the function of B cells to develop therapies that can mobilize the subset of B cells beneficial in MS to the brain and spinal cord with the aim to dampen the inflammation associated with MS.

Project Status: In Progress