Memory B cells from a subset of treatment-naive relapsing-remitting multiple sclerosis patients elicit CD4 super(+) T-cell proliferation and IFN- gamma production in response to myelin basic protein and myelin oligodendrocyte glycoprotein

• Published in: European journal of immunology 2010-10, Vol.40 (10), p.2942-2956
• Main Authors: Harp, Christopher T, Ireland, Sara, Davis, Laurie S, Remington, Gina, Cassidy, Bonnie, Cravens, Petra D, Stuve, Olaf, Lovett-Racke, Amy E, Eagar, Todd N, Greenberg, Benjamin M, Racke, Michael K, Cowell, Lindsay G, Karandikar, Nitin J, Frohman, Elliot M, Monson, Nancy L
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201040516

Recent evidence suggests that B- and T-cell interactions may be paramount in relapsing-remitting MS (RRMS) disease pathogenesis. We hypothesized that memory B-cell pools from RRMS patients may specifically harbor a subset of potent neuro-APC that support neuro-Ag reactive T-cell proliferation and cytokine secretion. To test this hypothesis, we compared CD80 and HLA-DR expression, IL-10 and lymphotoxin- alpha secretion, neuro-Ag binding capacity, and neuro-Ag presentation by memory B cells from RRMS patients to naive B cells from RRMS patients and to memory and naive B cells from healthy donors (HD). We identified memory B cells from some RRMS patients that elicited CD4 super(+) T-cell proliferation and IFN- gamma secretion in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Notwithstanding the fact that the phenotypic parameters that promote efficient Ag presentation were observed to be similar between RRMS and HD memory B cells, a corresponding capability to elicit CD4 super(+) T-cell proliferation in response to myelin basic protein and myelin oligodendrocyte glycoprotein was not observed in HD memory B cells. Our results demonstrate for the first time that the memory B-cell pool in RRMS harbors neuro-Ag specific B cells that can activate T cells.