Antibody titers and cardiac allograft survival in the sensitized rat model: Effect of time after initial sensitization
We examined the kinetics of alloantibody induced by skin grafting and the fate of cardiac allografts placed in acutely and remotely sensitized rats. These results indicate that over 6 months time a decline in circulating antibody titer sufficient to avoid immediate humoral rejection will occur, even following the potent sensitization of skin grafting and subsequent transplantation across a strong histocompatibility barrier. In addition to a decline in absolute amount of circulating immunoglobulin, some decrease in detectable antibody level may be due to the 'switch' from IgM to IgG synthesis. The former is more effective at hemagglutination, as well as more efficient at complement fixation. Since rat RBC display class I but not class II determinants, these results can only be assumed to reflect the kinetics of alloantibody to class I antigens. The kinetics of antibodies to class II and non-major histocompatibility complex determinants following sensitization are currently being investigated. The abrupt rise in alloantibody associated with rejection of allografts in group II, combined with the histologic findings consistent with humoral rejection, suggest that re-exposure of the recipient to ACI antigens via the cardiac allograft triggers an anamnestic B cell response with subsequent humoral rejection. At this point, effective methods for aborting this response are lacking. This model has not been previously described and may prove useful in testing methods aimed at eliminating sensitized B cells and their products.
Harland, RC; Knechtle, SJ; Yamaguchi, Y; Bollinger, RR
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