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The pathogenic role for B cells in the context of relapsing remitting multiple sclerosis (MS) is incompletely defined. Although classically considered a T cell-mediated disease, B cell-depleting therapies showed efficacy in treating the clinical symptoms of RRMS without decreasing plasma cells or total immunoglobulin (Ig) levels. Here, we discuss the potential implications of antibody-independent B cell effector functions that could contribute to autoimmunity with particular focus on antigen presentation, cytokine secretion, and stimulation of T cell subsets. We highlight differences between memory and naïve B cells from MS patients such as our recent findings of hyper-proliferation from MS memory B cells in response to CD40 engagement. We discuss the implications of IL6 overproduction in contrast to limited IL10 production by B cells from MS patients and comment on the impact of these functions on yet unexplored aspects of B cells in autoimmune disease. Finally, we contextualize B cell effector functions with respect to current immunomodulatory therapies for MS and show that glatiramer acetate (GA) does not directly modulate B cell proliferation or cytokine secretion.

The role of B cells in the pathogenesis of Multiple Sclerosis (MS) is incompletely understood. Here we define a possible role for B cells as myelin-specific antigen presenting cells (B-APCs) in MS. Peripheral blood B cells (PBBC) isolated from both MS patients and healthy controls (HC) were activated in vitro with either CD40L/IL-4 or a Class B CpG oligodeoxynucleotide (CpG ODN)/IL-2. Both activation techniques induced PBBCs to upregulate CD80 and HLA-DR, rendering them more efficient APCs than resting B cells. Although the CD40L/IL-4 B-APCs were highly effective in eliciting CNS-antigen specific proliferation by autologous T cells, CpG ODN/IL-2 stimulated B cells were not. Furthermore, CD40L/IL-4 B-APC induced responses by autologous CD4(+) T cells were susceptible to blocking with anti-HLA-DR antibody, suggesting that T cell responses were specific for antigen presentation by B-APC. CNS-antigen specific CD8(+) T cell proliferation was also blocked by HLA-DR, suggesting that CD8(+) proliferation is in part dependent on CD4(+) help.