Igg allo antibody responses to donor-specific blood transfusion in different rat strain combinations as a predictor of renal allograft survival

Donor-specific blood transfusion prolongs the survival of fully allogeneic ACI (RT1*) renal allografts in PVG (RT1°) recipients from 7-10 days to >100 days. We have observed significant differences in the alloan-tibody (AM) responses to ACI renal allografts in control and DSBT-treated PVG recipients: DSBT is associated with decreased IgG and IgM alloantibody circulating in serum, deposited in the allograft, and produced in culture by splenocytes. In the present studies the effects of DSBT on alloantibody production and renal allograft survival were extended to examine other recipient strains: F344 (RTllvl), BN (RT1"), W/F (RT1U) and LEW (RT11). Animals of each recipient strain were injected i.v. with 0.5 ml of ACI blood alone or followed by a renal allograft. Studies on the kinetics of IgM and IgG alloantibody responses were performed by flow cytometry on lymphocytes from donor ACI, PVG, and PVG.R1 (RTl.A* class IMHC antigen on PVG background) rats. In F344 and PVG rats, DSBT from ACI rats elicited a transient IgM response that peaked at day 7 and was not followed by a switch to IgG. In control PBS transfused F344 recipients, an ACI renal allograft stimulated both IgM and IgG alloantibody production. DSBT pretreatment significantly decreased circulating IgG alloantibody following ACI renal transplantation and prolonged graft survival in F344 recipients. In DSBT-treated F344 recipients that rejected ACI renal allografts acutely, small amounts of IgG (6-12 mode channel shift) were detected in sera harvested 7 days after transplantation, whereas almost no IgG was detected in the sera from DSBT treated F344 rats that accepted their renal allografts indefinitely. In contrast, DSBT alone from ACI to BN, W/F, or LEW strains elicited a transient IgM response that peaked at day 7 and was followed by a strong IgG response that peaked on days 10-14 and remained high through day 21. DSBT failed to prolong ACI renal allograft survival in any of these strains (survival DSBT pretreated allograft recipients > DSBT alone. Sera from DSBT-treated and transplanted F344 rats did not demonstrate blocking activity. These findings indicate that the IgG alloantibody response to RTl.A* class I MHC antigens following DSBT is predictive of subsequent renal allograft survival in these five fully MHC disparate strain combinations. This supports the possibility that DSBT-induced enhanced rat renal allografts survival is due to an inhibition of IgM to IgG switch in alloantibody production.