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Exosome-enriched fractions from MS B cells induce oligodendrocyte death

Joyce A Benjamins1, Liljana Nedelkoska1, Hanane Touil1

  • 1Departments of Neurology and Biochemistry, Immunology and Microbiology (J.A.B., R.P.L.), Wayne State University School of Medicine; Department of Neurology (L.N.), Wayne State University School of Medicine, Detroit, Michigan; Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (H.T., A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Neurology (H.T., A.B.-O.), McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada; Institute of Environmental Health Sciences (P.M.S., N.J.C.), Wayne State University; and Department of Physiology (B.P.J., A.R.N.), Wayne State University School of Medicine, Detroit, Michigan.

Neurology(R) Neuroimmunology & Neuroinflammation
|May 3, 2019
PubMed
Abstract

Insights

Extracellular microvesicles, specifically exosomes, from B cells of multiple sclerosis (MS) patients contain factors toxic to oligodendrocytes (OLs), unlike those from healthy individuals. Proteomic analysis reveals distinct exosome cargo in MS.

Area of Science:

  • Neuroimmunology
  • Cell Biology
  • Extracellular Vesicles

Background:

  • Multiple Sclerosis (MS) is a demyelinating disease where immune cells like B cells play a role.
  • Oligodendrocytes (OLs) are crucial for myelin sheath formation and are targets in MS pathogenesis.
  • Extracellular vesicles, including exosomes, are implicated in intercellular communication and disease processes.

Purpose of the Study:

  • To determine if B cell-derived extracellular microvesicles, enriched in exosomes, contain factors toxic to oligodendrocytes (OLs) in patients with MS.
  • To investigate the proteomic differences in exosomes released by B cells from MS patients compared to normal controls (NCs).

Main Methods:

  • B cell-conditioned medium from MS patients and NCs was used to isolate exosome-enriched (Ex-En) fractions via solvent precipitation, ultracentrifugation (UC), or immunoprecipitation (IP).
  • The toxicity of these Ex-En fractions on cultured rat OLs was assessed using trypan blue uptake.
  • Proteomic analysis was conducted on the conditioned medium fractions.

Main Results:

  • Ex-En fractions derived from MS patient B cells induced significant OL death, while fractions from NCs showed minimal toxicity.
  • Proteomic analysis confirmed the presence of exosome-characteristic proteins in both MS and NC B cell fractions.
  • Ontology enrichment analysis revealed differences in exosome cargo, with MS B cell exosomes showing enrichment in proteins related to cell surface, extracellular plasma membrane, and gliogenesis.

Conclusions:

  • A significant portion of the in vitro toxicity observed in B cell-conditioned medium from relapsing-remitting MS patients resides within exosome-enriched fractions.
  • Proteomic analysis highlights substantial differences in B cell-derived exosomes between MS patients and healthy individuals, suggesting a role in MS pathogenesis.

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