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A2.35 Glatiramer acetate restores the defective activity of regulatory B cells in SLE
  1. K Amrouche,
  2. JO Pers,
  3. S Hillion,
  4. C Jamin
  1. INSERM ERI29, EA2216, Immunology and Pathology, Université de Brest and the Université Européenne de Bretagne, Labex IGO, Immunotherapy, Graft, Oncology, CHRU de Brest, Brest, France

Abstract

Background and objectives Glatiramer Acetate (GA) is a synthetic pol ypeptide used in treatments of multiple sclerosis. Numerous studies have been performed to understand its effects on immune cells, but its role on B cells has been hardly described. Treatment of experimental autoimmune encephalomyelitis mice with GA has been shown to increase the frequency of CD5+CD1dHigh B cells known to develop regulatory function. The possibility therefore exists that GA might activate regulatory B (Breg) cells. The aim of our work was to evaluate the ability of GA to stimulate the regulatory functions of B cells in healthy individuals and to appraise its effect on SLE Breg cells known to be defective.

Materials and methods B cells were purified from SLE and healthy donors and stimulated for 4 h with GA. Autologous T cells were stimulated with anti-CD3 and anti-CD28 Abs. Their proliferation was evaluated by flow cytometry and the concomitant production of IFNgamma evaluated by ELISA. The regulatory activities of B cells on T cell responses were evaluated after 4 days in co-culture experiments. Phenotypical analyses by flow cytometry were performed using FITC-conjugated GA to identify the subsets of B cells able to catch the GA.

Results The proliferative response and the IFNgamma production of T cells from healthy donors were significantly decreased in the presence of GA-stimulated B cells compared to non-stimulated B cells. Interestingly, the defective regulatory activity of non-stimulated SLE B cells on SLE T cells was restored after 4-hour stimulation with GA before co-cultures. Memory B cells bound high level of FITC-conjugated GA in contrast to naïve B cells. After sorting and stimulation with GA, increased-GA dependent regulatory activities were specifically triggered in memory B cells and not naïve B cells.

Conclusions GA up-regulates the regulatory functions of B cells. These effects are mainly directed to the memory B cell pool. Specifically in SLE patients in which the Breg cells are defective and the memory B cell compartment abnormally elevated, our results suggest that GA treatment could restore the regulatory activity of the B cells and contribute to the efficacy of the GA-based therapeutics in autoimmune diseases.

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