Decreased levels of regulatory B cells in patients with systemic sclerosis: association with autoantibody production and disease activity

Rheumatology (Oxford). 2016 Feb;55(2):263-7. doi: 10.1093/rheumatology/kev331. Epub 2015 Sep 8.


Objective: B cell abnormalities characterized by autoantibody production and polyclonal B cell activation play an important role in the pathogenesis of SSc. IL-10 producing regulatory B (Breg) cells also play an important role in the negative immune response. We identified a human Breg cell subset that was predominantly found within the CD24(hi)CD27(+) B cell subpopulation. However, the role of Breg cells in SSc remains unknown. The aim of this study was to investigate the clinical association of Breg cells in SSc patients.

Methods: Blood IL-10 producing Breg cell levels were determined by FACS in 35 SSc patients and 30 healthy subjects. In a follow-up study, we analysed six individual dcSSc patients before and after treatment.

Results: The frequency of blood Breg cells was significantly lower in SSc patients than in healthy controls (P < 0.0001). Similarly, the frequency of CD24(hi)CD27(+) B cells was significantly lower in SSc patients than in healthy controls (P < 0.0001). SSc patients with decreased Breg cell levels often had interstitial lung disease (P < 0.05). Furthermore, Breg cell levels correlated negatively with the titre of anti-topo I antibody (Ab) and anticentromere Ab in SSc patients. For a follow-up study, Breg cell levels in dcSSc patients after treatment were found to be significantly increased compared with those before treatment (P < 0.05), accompanied by decreased disease activity. Thus, Breg cell levels were inversely correlated with disease activity of SSc.

Conclusion: These results suggest that decreased Breg cell levels may contribute to the development of SSc.

Keywords: IL-10; regulatory B cell; systemic sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies / biosynthesis*
  • Autoantibodies / immunology
  • Autoimmunity*
  • B-Lymphocytes, Regulatory / immunology*
  • B-Lymphocytes, Regulatory / metabolism
  • B-Lymphocytes, Regulatory / pathology
  • Disease Progression
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Interleukin-10 / metabolism
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / metabolism
  • Scleroderma, Systemic / pathology
  • Severity of Illness Index
  • Young Adult


  • Autoantibodies
  • Interleukin-10