Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spinal cord while preserving peripheral regulatory mechanisms

J Immunol. 2014 Nov 15;193(10):4823-32. doi: 10.4049/jimmunol.1401478. Epub 2014 Oct 3.


Plasma cells and the autoreactive Abs they produce are suspected to contribute to the pathogenesis of multiple sclerosis, but recent attempts to target these components of humoral immunity have failed. MEDI551, an anti-CD19 Ab that depletes mature B cells including plasma cells may offer a compelling alternative that reduces pathogenic adaptive immune responses while sparing regulatory mechanisms. Indeed, our data demonstrate that a single dose of MEDI551, given before or during ongoing experimental autoimmune encephalomyelitis, disrupts development of the disease. Leukocyte infiltration into the spinal cord is significantly reduced, as well as short-lived and long-lived autoreactive CD138(+) plasma cells in the spleen and bone marrow, respectively. In addition, potentially protective CD1d(hi)CD5(+) regulatory B cells show resistance to depletion, and myelin-specific Foxp3(+) regulatory T cells are expanded. Taken together, these results demonstrate that MEDI551 disrupts experimental autoimmune encephalomyelitis by inhibiting multiple proinflammatory components whereas preserving regulatory populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects*
  • Animals
  • Antibodies / pharmacology*
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology*
  • Antigens, CD1d / genetics
  • Antigens, CD1d / immunology
  • B-Lymphocytes, Regulatory / immunology
  • B-Lymphocytes, Regulatory / pathology
  • Bone Marrow / immunology*
  • Bone Marrow / pathology
  • Cell Survival
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Gene Expression
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Transgenic
  • Myelin-Oligodendrocyte Glycoprotein
  • Plasma Cells / immunology
  • Plasma Cells / pathology
  • Protein Engineering
  • Signal Transduction
  • Spinal Cord / immunology*
  • Spinal Cord / pathology
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology


  • Antibodies
  • Antigens, CD19
  • Antigens, CD1d
  • CD1d antigen, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Myelin-Oligodendrocyte Glycoprotein