| First Author | O'Neill SK | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 6 | Pages | 3781-8 |
| PubMed ID | 15749919 | Mgi Jnum | J:97700 |
| Mgi Id | MGI:3576152 | Doi | 10.4049/jimmunol.174.6.3781 |
| Citation | O'Neill SK, et al. (2005) Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis. J Immunol 174(6):3781-8 |
| abstractText | 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. |
