Autoreactive CD19+CD20- Plasma Cells Contribute to Disease Severity of Experimental Autoimmune Encephalomyelitis

J Immunol. 2016 Feb 15;196(4):1541-9. doi: 10.4049/jimmunol.1501376. Epub 2016 Jan 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD19 / immunology*
  • Antigens, CD20 / immunology*
  • Autoantibodies / analysis
  • B-Lymphocytes / immunology*
  • Cerebrospinal Fluid / chemistry
  • Cerebrospinal Fluid / cytology
  • Cerebrospinal Fluid / immunology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / therapy
  • Female
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Plasma Cells / immunology*


  • Antibodies, Monoclonal
  • Antigens, CD19
  • Antigens, CD20
  • Autoantibodies
  • Myelin-Oligodendrocyte Glycoprotein