Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis

EBioMedicine. 2017 Feb:16:41-50. doi: 10.1016/j.ebiom.2017.01.042. Epub 2017 Jan 31.

Abstract

Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells. This depletion was substantial and long-term following CD52 and CD20-depletion, and both also induced long-term inhibition of MS with few treatment cycles, indicating induction-therapy activity. Importantly, memory B cells were augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that are known to worsen MS. This creates a unifying concept centered on memory B cells that is consistent with therapeutic, histopathological and etiological aspects of MS.

Keywords: Autoimmunity; Disease modifying treatment; Immunotherapy; Memory B cell; Multiple sclerosis.

Publication types

  • Review

MeSH terms

  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Humans
  • Immunologic Memory / immunology*
  • Immunotherapy / methods*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Models, Immunological
  • Molecular Targeted Therapy / methods
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / therapy*
  • Plasma Cells / immunology
  • Plasma Cells / metabolism

Substances

  • Cytokines
  • Inflammation Mediators