Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis
| Autor: | Mark J. Shlomchik, Tibor T. Glant, Paul D. Doodes, Shannon K. O’Neill, Yanxia Cao, Alison Finnegan |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adoptive cell transfer
Transgene T-Lymphocytes Immunology Lymphocyte Cooperation Arthritis Antigen-Presenting Cells Mice Transgenic Mice SCID Lymphocyte Activation Autoantigens Mice medicine Immunology and Allergy Animals Receptor B cell Autoantibodies Cell Proliferation Autoimmune disease B-Lymphocytes Mice Inbred BALB C biology Genes Immunoglobulin business.industry Autoantibody medicine.disease Arthritis Experimental medicine.anatomical_structure Immunoglobulin M biology.protein Female Proteoglycans Antibody business |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 174(6) |
| ISSN: | 0022-1767 |
| Popis: | 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 λ 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. |
| Databáze: | OpenAIRE |
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