Critical Role of Sensitized Serum in Rejection of Allogeneic Bone Marrow Cells

Objective: Humoral immunity has been clearly implicated in solid organ transplantation, but little is known about the relationship between humoral immunity and hematopoietic stem cell transplantation. This study was designed to investigate that relationship. Materials and Methods: Sensitized serum was obtained from a sensitized murine model established by allogeneic splenocyte transfusion. Sensitized serum was incubated with allogeneic bone marrow cells (BMCs) in vitro and the cytotoxicity was evaluated by the complement-dependent cytotoxicity method. Mice were transplanted with allogeneic BMCs incubated with sensitized serum after lethal irradiation. The engraftment was assayed by hematopoietic recovery and chimera analysis. Moreover, mice received passive transfer of sensitized serum 1 day prior to transplantation. Mortality was scored daily after bone marrow transplantation. Results: The in vitro experiments showed that sensitized serum was capable of impairing allogeneic BMCs through the complement-dependent cytotoxicity pathway. The animal studies showed that BMCs incubated with sensitized serum failed to rescue mice from lethal irradiation. The engraftment assay showed that the allogeneic BMCs incubated with sensitized serum were rejected with time in the recipients. Furthermore, the mice died of marrow graft rejection by transfer of sensitized serum prior to transplantation. Conclusion: Taken together, our results indicated that sensitized serum played a critical role in graft rejection during hematopoietic stem cell transplantation.