Allogeneic BMT can effectively treat CIA, a severe B cell-mediated autoimmune disease. (A) Allogeneic and syngeneic BMT have a suppressive effect on arthritis after nonmyeloablative conditioning (^**P = .007 and ^**P = .001, respectively). Clinical data of arthritic DBA/1 mice (n = 8 mice per group) treated with sublethal TBI of 6.0 Gy (day 37) plus a single injection of anti-CD40L mAb (0.5 mg intraperitoneally, day 38) and subsequently injected with 1.0 × 10⁷ total BM cells intravenously from syngeneic DBA/1 mice or fully major histocompatibility complex (MHC)-mismatched allogeneic BALB/c mice are shown (day 38; arrow indicates start of treatment). No statistical differences were observed at the time of treatment. Results from 1 of 2 experiments are shown. (B) Allogeneic BMT results in a marked decrease of pathogenic anti-type II collagen autoantibodies. Sera were taken at 2 and 6 weeks after BMT (days 52 and 81, respectively) and were tested by ELISA for the presence of anti-type II collagen antibodies (data are shown for the IgG2a isotype). Allogeneic BMT was more effective in suppressing the production of anti-type II collagen antibodies (^**P < .002) than syngeneic BMT or conditioning alone (^*P < .05) compared with untreated animals. Allogeneic BMT compared with syngeneic BMT and conditioning alone (^*P = .02) at 6 weeks after BMT. (C) Anti-type II collagen antibodies after allogeneic BMT are of recipient origin. None of the allogeneic BMT recipients developed anti-type II collagen antibodies of the Igh-1a allotype, demonstrating that the antibodies present after allogeneic BMT are of recipient origin. As positive and negative controls for the presence of Igh-1a, we immunized normal BALB/c and DBA/1 mice, respectively, with CII. Immunized BALB/c mice were able to produce CII-specific antibodies to the same extent as immunized DBA/1 mice without the clinical symptoms of arthritis (data not shown).