Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-γ production in response to myelin basic protein and myelin oligodendrocyte glycoprotein.
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-α secretion, neuro-Ag binding capacity, and neuro-Ag presentation by memory B cells from RRMS patients to naïve B cells from RRMS patients and to memory and naïve B cells from healthy donors (HD). We identified memory B cells from some RRMS patients that elicited CD4(+) T-cell proliferation and IFN-γ 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(+) 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.
Harp
Christopher T
CT
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ireland
Sara
S
Davis
Laurie S
LS
Remington
Gina
G
Cassidy
Bonnie
B
Cravens
Petra D
PD
Stuve
Olaf
O
Lovett-Racke
Amy E
AE
Eagar
Todd N
TN
Greenberg
Benjamin M
BM
Racke
Michael K
MK
Cowell
Lindsay G
LG
Karandikar
Nitin J
NJ
Frohman
Elliot M
EM
Monson
Nancy L
NL
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D055815:Young Adult
D008233:Lymphotoxin-alpha; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D007371:Interferon-gamma
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