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B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis
  1. Laetitia Rapetti,
  2. Konstantia-Maria Chavele,
  3. Catherine M Evans,
  4. Michael R Ehrenstein
  1. Division of Medicine, Centre for Rheumatology, University College London, London, UK
  1. Correspondence to Professor Michael R Ehrenstein, Division of Medicine, Centre for Rheumatology, University College London, London, WC1E 6JF, UK; m.ehrenstein{at}ucl.ac.uk

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.

  • Rheumatoid Arthritis
  • B cells
  • T Cells
  • Autoimmunity

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