Frontiers in Immunology (Nov 2020)

Identification of CD137-Expressing B Cells in Multiple Sclerosis Which Secrete IL-6 Upon Engagement by CD137 Ligand

  • Hiu Yi Wong,
  • Hiu Yi Wong,
  • Ankshita Prasad,
  • Shu Uin Gan,
  • John Jia En Chua,
  • John Jia En Chua,
  • John Jia En Chua,
  • Herbert Schwarz,
  • Herbert Schwarz

DOI
https://doi.org/10.3389/fimmu.2020.571964
Journal volume & issue
Vol. 11

Abstract

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The potent costimulatory effect of CD137 has been implicated in several murine autoimmune disease models. CD137 costimulates and polarizes antigen-specific T cells toward a potent Th1/Tc1 response, and is essential for the development of experimental autoimmune encephalomyelitis (EAE), a murine model of Multiple Sclerosis (MS). This study aimed to investigate a role of CD137 in MS. Immunohistochemical and immunofluorescence staining of MS brain tissues was used to identify expression of CD137. CD137+ cells were identified in MS brain samples, with active lesions having the highest frequency of CD137+ cells. CD137 expression was found on several leukocyte subsets, including T cells, B cells and endothelial cells. In particular, CD137+ B cells were found in meningeal infiltrates. In vitro experiments showed that CD137 engagement on activated B cells increased early TNF and persistent IL-6 secretion with increased cell proliferation. These CD137+ B cells could interact with CD137L-expressing cells, secrete pro-inflammatory cytokines and accumulate in the meningeal infiltrate. This study demonstrates CD137 expression by activated B cells, enhancement of the inflammatory activity of B cells upon CD137 engagement, and provides evidence for a pathogenic role of CD137+ B cells in MS.

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