Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis

J Immunol. 2005 Mar 15;174(6):3781-8. doi: 10.4049/jimmunol.174.6.3781.

Abstract

B cells play an important role in rheumatoid arthritis, but whether they are required as autoantibody-producing cells as well as APCs has not been determined. We assessed B cell autoantibody and APC functions in a murine model of autoimmune arthritis, proteoglycan (PG)-induced arthritis, using both B cell-deficient mice and Ig-deficient mice (mIgM) mice that express an H chain transgene encoding for membrane-bound, but not secreted, IgM. The IgH transgene, when paired with endogenous lambda L chain, recognizes the hapten 4-hydroxy-3-nitro-phenyl acetyl and is expressed on 1-4% of B cells. B cell-deficient and mIgM mice do not develop arthritis after immunization with PG. In adoptive transfer of PG-induced arthritis into SCID mice, T cells from mIgM mice immunized with PG were unable to transfer disease even when B cells from PG-immunized wild-type mice were provided, suggesting that the T cells were not adequately primed and that Ag-specific B cells may be required. In fact, when PG was directly targeted to the B cell Ig receptor through a conjugate of 4-hydroxy-3-nitrophenyl acetyl-PG, T cells in mIgM mice were activated and competent to transfer arthritis. Such T cells caused mild arthritis in the absence of autoantibody, demonstrating a direct pathogenic role for T cells activated by Ag-specific B cells. Transfer of arthritic serum alone induced only mild and transient arthritis. However, both autoreactive T cells and autoantibody are required to cause severe arthritis, indicating that both B cell-mediated effector pathways contribute synergistically to autoimmune disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Arthritis, Experimental / etiology*
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology
  • Autoantibodies / biosynthesis*
  • Autoantigens / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Cell Proliferation
  • Female
  • Genes, Immunoglobulin
  • Immunoglobulin M / genetics
  • Immunoglobulin M / metabolism
  • Lymphocyte Activation
  • Lymphocyte Cooperation
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mice, Transgenic
  • Proteoglycans / immunology
  • T-Lymphocytes / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • Immunoglobulin M
  • Proteoglycans