Glatiramer acetate immune modulates B-cell antigen presentation in treatment of MS

Neurol Neuroimmunol Neuroinflamm. 2020 Mar 17;7(3):e698. doi: 10.1212/NXI.0000000000000698. Print 2020 May.

Abstract

Objective: We examined the effect of glatiramer acetate (GA) on B-cell maturation, differentiation, and antigen presentation in MS and experimental autoimmune encephalomyelitis (EAE).

Methods: A cross-sectional study of blood samples from 20 GA-treated and 18 untreated patients with MS was performed by flow cytometry; 6 GA-treated patients with MS were analyzed longitudinally. GA-mediated effects on B-cell antigen-presenting function were investigated in EAE, or, alternatively, B cells were treated with GA in vitro using vehicle as a control.

Results: In MS, GA diminished transitional B-cell and plasmablast frequency, downregulated CD69, CD25, and CD95 expression, and decreased TNF-α production, whereas IL-10 secretion and MHC Class II expression were increased. In EAE, we observed an equivalent dampening of proinflammatory B-cell properties and an enhanced expression of MHC Class II. When used as antigen-presenting cells for activation of naive T cells, GA-treated B cells promoted development of regulatory T cells, whereas proinflammatory T-cell differentiation was diminished.

Conclusions: GA immune modulates B-cell function in EAE and MS and efficiently interferes with pathogenic B cell-T cell interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigen-Presenting Cells / drug effects*
  • B-Lymphocytes / drug effects*
  • Cross-Sectional Studies
  • Encephalomyelitis, Autoimmune, Experimental / blood
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Female
  • Flow Cytometry
  • Glatiramer Acetate / pharmacology*
  • Humans
  • Immunologic Factors / pharmacology*
  • Longitudinal Studies
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*

Substances

  • Immunologic Factors
  • Glatiramer Acetate