B cell antigen presentation is sufficient to drive neuro-inflammation in an animal model of multiple sclerosis1

• Published in: The Journal of immunology (1950) Vol. 194; no. 11; pp. 5077 - 5084
• Main Authors: Parker Harp, Chelsea R., Archambault, Angela S., Sim, Julia, Ferris, Stephen T., Mikesell, Robert J., Koni, Pandelakis A., Shimoda, Michiko, Linington, Christopher, Russell, John H., Wu, Gregory F.
• Format: Journal Article
• Language: English
• Published: 20.04.2015
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1402236

B cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis (MS) in part due to the success of B cell depletion therapy. Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the central nervous system (CNS) have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis (MS). While B cell antigen presentation has been suggested to regulate CNS inflammation during EAE, direct evidence that B cells can independently support antigen-specific autoimmune responses by CD4 T cells in EAE is lacking. Using a newly developed murine model of in vivo conditional expression of MHCII, we previously reported that encephalitogenic CD4 T cells are incapable of inducing EAE when B cells are the sole antigen presenting cell. Herein we find that B cells cooperate with dendritic cells to enhance EAE severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Further, increasing the precursor frequency of MOG-specific B cells, but not addition of soluble MOG-specific antibody, is sufficient to drive EAE in mice expressing MHCII by B cells alone. These data support a model in which expansion of antigen-specific B cells during CNS autoimmunity amplifies cognate interactions between B and CD4 T cells and have the capacity to independently drive neuro-inflammation at later stages of disease.