B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells

B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6-secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell-specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated…

• B
  Biogen
• WT
  Wellcome Trust
• MS
  Multiple Sclerosis Society of Canada
• MS
  Multiple Sclerosis Society
• DF
  Deutsche Forschungsgemeinschaft

  Award: SFB-650
• CI
  Canadian Institutes of Health Research
• MR
  Medical Research Council