TY - JOUR
T1 - B-Cell Depletion Abrogates T Cell-Mediated Demyelination in an Antibody-Nondependent Common Marmoset Experimental Autoimmune Encephalomyelitis Model
AU - Jagessar, Anwar
AU - Heijmans, N
AU - Bauer, J
AU - Blezer, ELA
AU - Laman, Jon
AU - Hellings, N
AU - Hart, Boris
PY - 2012
Y1 - 2012
N2 - CD20-positive B-cell depletion is a highly promising treatment for multiple sclerosis (MS), but the mechanisms underlying therapeutic effects are poorly understood. B cells are thought to contribute to MS pathogenesis by producing autoantibodies that amplify demyelination via opsonization of myelin. To analyze autoantibody-nondependent functions of B cells in an animal model of MS, we used a novel T cell-driven experimental autoimmune encephalomyelitis (EAE) model in marmoset monkeys (Callithrix jacchus). In this model, demyelination of brain and spinal cord white and gray matter and the ensuing neurological deficits are induced by immunization with peptide 34 to 56 of myelin/oligodendrocyte glycoprotein (MOG(34) (56)) in incomplete Freund's adjuvant. Although autoantibodies do not have a detectable pathogenic contribution in the model, depletion of B cells with monoclonal antibody 7D8, a human IgG1 kappa monoclonal antibody against human CD20, suppressed clinical and pathological EAE. In B cell-depleted monkeys, the activation of peptide-specific Th17-producing and cytotoxic T cells, which in previous studies were found to play an essential role in disease induction, was impaired. Thus, we demonstrate a critical antibody-nondependent role for B cells in EAE, that is, the activation of pathogenic T cells.
AB - CD20-positive B-cell depletion is a highly promising treatment for multiple sclerosis (MS), but the mechanisms underlying therapeutic effects are poorly understood. B cells are thought to contribute to MS pathogenesis by producing autoantibodies that amplify demyelination via opsonization of myelin. To analyze autoantibody-nondependent functions of B cells in an animal model of MS, we used a novel T cell-driven experimental autoimmune encephalomyelitis (EAE) model in marmoset monkeys (Callithrix jacchus). In this model, demyelination of brain and spinal cord white and gray matter and the ensuing neurological deficits are induced by immunization with peptide 34 to 56 of myelin/oligodendrocyte glycoprotein (MOG(34) (56)) in incomplete Freund's adjuvant. Although autoantibodies do not have a detectable pathogenic contribution in the model, depletion of B cells with monoclonal antibody 7D8, a human IgG1 kappa monoclonal antibody against human CD20, suppressed clinical and pathological EAE. In B cell-depleted monkeys, the activation of peptide-specific Th17-producing and cytotoxic T cells, which in previous studies were found to play an essential role in disease induction, was impaired. Thus, we demonstrate a critical antibody-nondependent role for B cells in EAE, that is, the activation of pathogenic T cells.
U2 - 10.1097/NEN.0b013e3182622691
DO - 10.1097/NEN.0b013e3182622691
M3 - Article
C2 - 22805775
SN - 0022-3069
VL - 71
SP - 716
EP - 728
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 8
ER -