Suppression of proteoglycan-induced arthritis by anti-CD20 B Cell depletion therapy is mediated by reduction in autoantibodies and CD4+ T cell reactivity

J Immunol. 2008 Apr 1;180(7):4994-5003. doi: 10.4049/jimmunol.180.7.4994.


B cells have been implicated in the pathogenesis of rheumatoid arthritis (RA) since the discovery of RA as an autoimmune disease. There is renewed interest in B cells in RA based on the clinical efficacy of B cell depletion therapy in RA patients. Although, reduced titers of rheumatoid factor and anti-cyclic citrullinated peptide Abs are recorded, the mechanisms that convey clinical improvement are incompletely understood. In the proteoglycan-induced arthritis (PGIA) mouse model of RA, we reported that Ag-specific B cells have two important functions in the development of arthritis. PG-specific B cells are required as autoantibody-producing cells as well as Ag-specific APCs. Herein we report on the effects of anti-CD20 mAb B cell depletion therapy in PGIA. Mice were sensitized to PG and treated with anti-CD20 Ab at a time when PG-specific autoantibodies and T cell activation were evident but before acute arthritis. In mice treated with anti-CD20 mAb, development of arthritis was significantly reduced in comparison to control mAb-treated mice. B cell depletion reduced the PG-specific autoantibody response. Furthermore, there was a significant reduction in the PG-specific CD4(+) T cell recall response as well as significantly fewer PG-specific CD4(+) T cells producing IFN-gamma and IL-17, but not IL-4. The reduction in PG-specific T cells was confirmed by the inability of CD4(+) T cells from B cell-depleted mice to adoptively transfer disease into SCID mice. Overall, B cell depletion during PGIA significantly reduced disease and inhibited both autoreactive B cell and T cell function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD20 / immunology*
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / therapy*
  • Autoantibodies / immunology*
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Female
  • Immunotherapy
  • Mice
  • Proteoglycans / pharmacology*


  • Antibodies, Monoclonal
  • Antigens, CD20
  • Autoantibodies
  • Proteoglycans