Immune response in immunized FVIII^null mice. (A) FVIII^null mice received 4 weekly intravenous injections of recombinant human B-domain deleted FVIII (rhBDDFVIII) to a final plasma level of 1 U/mL. One week after the last immunization, mice received whole body irradiation at either 1100 cGy or 660 cGy followed by BM transplantation from 2bF8^tg+/− mice. Plasma was collected and inhibiter titer was determined by Bethesda assay at various time points. Bars represent mean plus or minus SD. Data shown are summarized from 7 BM transplantation trials. (B) Inhibitory plasma from immunized FVIII^null mice was infused into FVIII^null mice, and then plasma was collected at days 1, 7, and 14. The residual inhibitor titer was determined by Bethesda assay to define the half-life (t_1/2) of inhibitory antibody clearance (in the absence of additional antibody production). These results demonstrate that inhibitory antibodies continue to be produced in recipients even after lethal irradiation.