title: Autoreactive CD19+CD20- Plasma Cells Contribute to Disease Severity of Experimental Autoimmune Encephalomyelitis.
abstract: The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we reported that MEDI551, an anti-CD19 mAb, therapeutically ameliorates experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. MEDI551 potently inhibits pathogenic adaptive immune responses, including depleting autoantibody-producing plasma cells. In the present study, we demonstrated that CD19 mAb treatment ameliorates EAE more effectively than does CD20 mAb. Myelin oligodendrocyte glycoprotein-specific Abs and short-lived and long-lived autoantibody-secreting cells were nearly undetectable in the CD19 mAb-treated mice, but they remained detectable in the CD20 mAb-treated mice. Interestingly, residual disease severity in the CD20 mAb-treated animals positively correlated with the frequency of treatment-resistant plasma cells in the bone marrow. Of note, treatment-resistant plasma cells contained a substantial proportion of CD19(+)CD20(-) plasma cells, which would have otherwise been targeted by CD19 mAb. These data suggested that CD19(+)CD20(-) plasma cells spared by anti-CD20 therapy likely contribute to residual EAE severity by producing autoreactive Abs. In patients with MS, we also identified a population of CD19(+)CD20(-) B cells in the cerebrospinal fluid that would be resistant to CD20 mAb treatment.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas TX 75390;
authors.forename: Ding
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas TX 75390;
authors.forename: Sara J
authors.identifier: http://orcid.org/0000-0002-7811-197X
authors.initials: SJ
authors.lastname: Ireland
authors.affiliation: Rheumatic Diseases Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Laurie S
authors.initials: LS
authors.lastname: Davis
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas TX 75390;
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas TX 75390;
authors.forename: Ann M
authors.identifier: http://orcid.org/0000-0001-8111-4429
authors.initials: AM
authors.lastname: Stowe
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, MD 20878;
authors.forename: Yue
authors.identifier: http://orcid.org/0000-0003-0802-1140
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Translational Science Department, MedImmune LLC, Gaithersburg, MD 20878; and.
authors.forename: Wendy I
authors.initials: WI
authors.lastname: White
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, MD 20878;
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas TX 75390; Department of Immunology, University of Texas Southwestern Medical Center, Dallas TX 75390 nancy.monson@utsouthwestern.edu.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Monson
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology*; D018951:Antigens, CD20 / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D018951:Antigens, CD20; D001323:Autoantibodies; D063308:Myelin-Oligodendrocyte Glycoprotein