title: B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate whether regulatory T cells (Treg) can control B cell function in rheumatoid arthritis (RA) and if not to explore the basis for this defect.
  
  
  METHODS
  Suppression of B cell responses by Treg was analysed in vitro by flow cytometry and ELISA using peripheral blood mononuclear cells from 65 patients with RA and 41 sex-matched and aged-matched healthy volunteers. Blocking and agonistic antibodies were used to define the role of Fas-mediated apoptosis in B cell regulation.
  
  
  RESULTS
  Treg failed to restrain B cell activation, proinflammatory cytokine and antibody production in the presence of responder T cells in RA patients. This lack of suppression was not only caused by impaired Treg function but was also due to B cell resistance to regulation. In healthy donors, control by Treg was associated with increased B cell death and relied upon Fas-mediated apoptosis. In contrast, RA B cells had reduced Fas expression compared with their healthy counterparts and were resistant to Fas-mediated apoptosis.
  
  
  CONCLUSIONS
  These studies demonstrate that Treg are unable to limit B cell responses in RA. This appears to be primarily due to B cell resistance to suppression, but Treg defects also contribute to this failure of regulation. Our data identify the Fas pathway as a novel target for Treg-mediated suppression of B cells and highlight a potential therapeutic approach to restore control of B cells by Treg in RA patients.
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London, UK.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Rapetti
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London, UK.
authors.forename: Konstantia-Maria
authors.initials: KM
authors.lastname: Chavele
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London, UK.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Evans
authors.affiliation: Division of Medicine, Centre for Rheumatology, University College London, London, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ehrenstein
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D019014:fas Receptor
keywords: Autoimmunity; B cells; Rheumatoid Arthritis; T Cells