B-cell depletion abrogates T cell-mediated demyelination in an antibody-nondependent common marmoset experimental autoimmune encephalomyelitis model.
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 (MOG34-56) in incomplete Freund's adjuvant. Although autoantibodies do not have a detectable pathogeniccontribution in the model, depletion of B cells with monoclonal antibody 7D8, a human IgG1κ 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.
Department Immunobiology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
S Anwar
SA
Jagessar
Nicole
N
Heijmans
Jan
J
Bauer
Erwin L A
EL
Blezer
Jon D
JD
Laman
Niels
N
Hellings
Bert A
BA
't Hart
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D001921:Brain / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D019002:CD56 Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002144:Callithrix / Q000502:physiology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D007114:Immunization; D008212:Lymphocyte Depletion / Q000009:adverse effects*; D009185:Myelin Proteins / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010641:Phenotype; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D019002:CD56 Antigen; D016207:Cytokines; C571326:MOG protein, human; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011994:Recombinant Proteins