title: Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity.
abstract: OBJECTIVE
  Regulatory interleukin-10 (IL-10)-producing B cells (B10 cells) have been shown to prevent and cure collagen-induced arthritis in mice. In humans, very little is known about B10 cells in rheumatoid arthritis (RA). Several B cell subsets, such as CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells, were suggested to be precursors of B10 cells. We aimed to analyze these B cell subsets and B10 cells in RA patients and healthy controls.
  
  
  METHODS
  B10 cells were generated from peripheral blood mononuclear cells stimulated for 24 hours with CpG and for 4 hours with phorbol 12-myristate 13-acetate/ionomycin/brefeldin A. Intracellular B cell IL-10 was assessed by flow cytometry. Thirty-one controls and 99 RA patients were included.
  
  
  RESULTS
  After multiple adjustments, levels of CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells were found to be similar in RA patients and controls. Levels of B10 cells were lower in RA patients than in controls, especially in patients with RA of ≤5 years' duration. Levels of B10 cells correlated inversely with the Disease Activity Score in 28 joints. This was more pronounced in patients with RA of ≤5 years' duration, in whom B10 cells also correlated inversely with C-reactive protein levels. Moreover, B10 cells correlated inversely with rheumatoid factor levels. CD24(high) CD38(high) and CD24(high) CD27+ B cells induced more Treg cells than did CD24(low) B cells in controls but not in RA patients.
  
  
  CONCLUSIONS
  The ability of B cells to produce IL-10 was altered in RA, and this impairment influenced disease activity, biologic inflammation, and autoantibody levels, especially in patients with RA of ≤5 years' duration. This strongly suggests a role of B10 cells in RA initiation.
authors.affiliation: Lapeyronie Hospital, Montpellier 1 University, and Institute of Molecular Genetics of Montpellier, UMR5535, CNRS, Montpellier, France.
authors.forename: Claire I
authors.initials: CI
authors.lastname: Daien
authors.forename: Sarah
authors.initials: S
authors.lastname: Gailhac
authors.forename: Thibault
authors.initials: T
authors.lastname: Mura
authors.forename: Rachel
authors.initials: R
authors.lastname: Audo
authors.forename: Bernard
authors.initials: B
authors.lastname: Combe
authors.forename: Michael
authors.initials: M
authors.lastname: Hahne
authors.forename: Jacques
authors.initials: J
authors.lastname: Morel
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged
chemical_list: D016753:Interleukin-10