title: B-cell depletion attenuates white and gray matter pathology in marmoset experimental autoimmune encephalomyelitis.
abstract: This study investigated the effect of CD20-positive B-cell depletion on central nervous system (CNS) white and gray matter pathology in experimental autoimmune encephalomyelitis in common marmosets, a relevant preclinical model of multiple sclerosis. Experimental autoimmune encephalomyelitis was induced in 14 marmosets by immunization with recombinant human myelin oligodendrocyte glycoprotein in complete Freund adjuvant. At 21 days after immunization, B-cell depletion was achieved by weekly intravenous injections of HuMab 7D8, a human-anti-human CD20 antibody that cross-reacts with marmoset CD20. In vivo magnetic resonance imaging showed widespread brain white matter demyelination in control marmosets that was absent in CD20 antibody-treated marmosets. High-contrast postmortem magnetic resonance imaging showed white matter lesions in 4of the 7 antibody-treated marmosets, but these were significantly smaller than those in controls. The same technique revealed gray matter lesions in 5 control marmosets, but none in antibody-treated marmosets. Histologic analysis confirmed that inflammation, demyelination, and axonal damage were substantially reduced in brain, spinal cord, and optic nerves of CD20 antibody-treated marmosets. In conclusion, CD20-postive B-cell depletion by HuMab 7D8 profoundly reduced the development of both white and gray matter lesions in the marmoset CNS. These data underline the central role of B cells in CNS inflammatory-demyelinating disease.
authors: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk. kap@bprc.nl
authors: Yolanda S
authors: YS
authors: Kap
authors: Jan
authors: J
authors: Bauer
authors: Nikki van
authors: Nv
authors: Driel
authors: Wim K
authors: WK
authors: Bleeker
authors: Paul W H I
authors: PW
authors: Parren
authors: Evert-Jan
authors: EJ
authors: Kooi
authors: Jeroen J G
authors: JJ
authors: Geurts
authors: Jon D
authors: JD
authors: Laman
authors: Jenny L
authors: JL
authors: Craigen
authors: Erwin
authors: E
authors: Blezer
authors: Bert A
authors: BA
authors: 't Hart
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D040502:Calgranulin B / Q000378:metabolism; D002144:Callithrix; D003186:Complement C9 / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D005620:Freund's Adjuvant / Q000009:adverse effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009185:Myelin Proteins / Q000009:adverse effects; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D018709:Statistics, Nonparametric; D060245:Tetraspanin 29 / Q000378:metabolism
chemical_list: D000906:Antibodies; D018951:Antigens, CD20; D040502:Calgranulin B; D003186:Complement C9; D000949:Histocompatibility Antigens Class II; C571326:MOG protein, human; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016900:Neurofilament Proteins; D060245:Tetraspanin 29; C051774:neurofilament protein H; D005620:Freund's Adjuvant