The Role of B Cells in Primary Progressive Multiple Sclerosis

Jameson P. Holloman, Robert C. Axtell, Nancy L. Monson, Gregory F. Wu

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

The success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease progression in PPMS, specifically exploring cytokine production, antigen presentation, and antibody synthesis. B cells may contribute to disease progression in PPMS through cytokine production, specifically GM-CSF and IL-6, which can drive naïve T-cell differentiation into pro-inflammatory Th1/Th17 cells. B cell production of the cytokine LT-α may induce follicular dendritic cell production of CXCL13 and lead indirectly to T and B cell infiltration into the CNS. In contrast, production of IL-10 by B cells likely induces an anti-inflammatory effect that may play a role in reducing neuroinflammation in PPMS. Therefore, reduced production of IL-10 may contribute to disease worsening. B cells are also capable of potent antigen presentation and may induce pro-inflammatory T-cell differentiation via cognate interactions. B cells may also contribute to disease activity via antibody synthesis, although it's unlikely the benefit of ocrelizumab in PPMS occurs via antibody decrement. Finally, various B cell subsets likely promulgate pro- or anti-inflammatory effects in MS.

Original languageEnglish (US)
Article number680581
JournalFrontiers in Neurology
Volume12
DOIs
StatePublished - Jun 7 2021

Keywords

  • B cell
  • immune pathogenesis
  • inflammation
  • multiple sclerosis
  • primary progressive multiple sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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