A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell-mediated and humoral immune responses

Int Immunol. 2006 Oct;18(10):1473-85. doi: 10.1093/intimm/dxl080. Epub 2006 Aug 16.


BAFF [B cell-activating factor of the tumour necrosis factor (TNF) family] and APRIL (a proliferation-inducing ligand) are two TNF family members with shared receptors. While, physiological roles for APRIL are not fully understood, BAFF is critical for B cell homeostasis and also acts as a co-stimulator of T cells. Using a B and T cell-mediated mouse model of multiple sclerosis (MS), myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), we observed that a BAFF/APRIL antagonist (soluble BCMA-Fc) inhibited central nervous system inflammation and demyelination such that it suppressed the onset and progression of clinical symptoms of EAE. In addition to dramatically reducing the titre of MOG-specific auto-antibodies, this treatment also induced a switch in the subtype of the T(h) cell population characterized by marked alterations in cytokine production following re-stimulation with MOG in vitro. Indeed, hBCMA-Fc therapy led to significant increases in the level of transforming growth factor beta, while the levels of T(h)1 cytokines were markedly diminished. These results not only identify BAFF as a critical factor in maintaining humoral immunity in EAE but also support its role in T lymphocyte responses. Our findings demonstrate that hBCMA-Fc acts on both effector arms of the immune response in EAE, a characteristic that may be of significant therapeutic value in the treatment of MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / drug effects*
  • Antibody Formation / immunology
  • B-Cell Activating Factor / antagonists & inhibitors*
  • B-Cell Activating Factor / immunology
  • B-Cell Maturation Antigen / administration & dosage*
  • B-Lymphocytes / immunology
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Immunoglobulin Fc Fragments / administration & dosage*
  • Mice
  • Mice, Inbred NOD
  • Multiple Sclerosis / chemically induced
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / administration & dosage
  • Myelin-Associated Glycoprotein / toxicity
  • Myelin-Oligodendrocyte Glycoprotein
  • Recombinant Fusion Proteins / administration & dosage
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / antagonists & inhibitors
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology


  • B-Cell Activating Factor
  • B-Cell Maturation Antigen
  • Immunoglobulin Fc Fragments
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Recombinant Fusion Proteins
  • Tnfrsf17 protein, mouse
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 13