title: Antibody-independent B cell effector functions in relapsing remitting multiple sclerosis: clues to increased inflammatory and reduced regulatory B cell capacity.
abstract: 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.
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Ireland
authors.forename: Monica
authors.initials: M
authors.lastname: Blazek
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Harp
authors.forename: Benjamin
authors.initials: B
authors.lastname: Greenberg
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
authors.forename: Laurie S
authors.initials: LS
authors.lastname: Davis
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Monson
mesh_terms: D000906:Antibodies / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D016207:Cytokines