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Research Article

Antibody-independent B cell effector functions in relapsing remitting Multiple Sclerosis: Clues to increased inflammatory and reduced regulatory B cell capacity

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Pages 400-414 | Received 16 Jan 2012, Accepted 07 Feb 2012, Published online: 18 Apr 2012
 

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.

Acknowledgements

The authors wish to thank the MS patients and healthy donors who have contributed samples to these studies. We also thank the CONQUER repository team and the UTSWMC FLOW CYTOMETRY CORE for their support in obtaining samples and collecting data for these studies. Finally, we thank TEVA Neuroscience for supporting the B-T project for the past 5 years.

Declaration of Interest: Dr. Nancy Monson is a paid consultant for MedImmune, and serves as a scientific advisor for Genentech. Funding for this project is provided by TEVA Neuroscience. The authors have no other interests to declare. The authors alone are responsible for the content and writing of the paper.

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