B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis

Exp Neurol. 2010 Jan;221(1):136-45. doi: 10.1016/j.expneurol.2009.10.015. Epub 2009 Oct 29.


Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) thought to be primarily mediated by T cells. However, emerging evidence supports an important role for B cells in the pathogenesis and inhibition of MS. Glatiramer acetate (GA), a Food and Drug Administration-approved drug for the treatment of MS, has a good safety profile. But GA's mechanism of action in MS is still elusive. In this study, we showed that B cells from GA-treated mice increased production of IL-10 and reduced expression of co-stimulatory molecules viz.: CD80 and CD86. B cells from GA-treated mice also diminished proliferation of myelin oligodendrocyte glycoprotein (MOG(35-55)) specific T cells. Purified B cells transferred from GA-treated mice suppressed experimental autoimmune encephalomyelitis (EAE) in recipient mice compared with B cells transferred from mice treated with PBS or ovalbumin. The treatment effect of GA in EAE was abrogated in B cell-deficient mice. Transfer of B cells from GA-treated mice inhibited the proliferation of autoreactive T cells as well as the development of Th1 and Th17 cells but promoted IL-10 production in recipient mice. The number of peripheral CD11b(+) macrophages in recipient mice also decreased after transfer of B cells from GA-treated mice; however, the number of dendritic cells and regulatory T cells remained unaltered. These results suggest that B cells are important to the protective effects of GA in EAE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • Antigens, CD / metabolism
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / physiology*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Flow Cytometry / methods
  • Gene Expression Regulation / physiology
  • Glatiramer Acetate
  • Glycoproteins
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / genetics
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Peptides / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Transforming Growth Factor beta / metabolism


  • Antigens, CD
  • Glycoproteins
  • Immunosuppressive Agents
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Peptides
  • Transforming Growth Factor beta
  • myelin oligodendrocyte glycoprotein (35-55)
  • Interleukin-10
  • Interleukin-4
  • Glatiramer Acetate