Primarily vascularized LBN cardiac allografts transplanted to LEW rats are rejected 6 to 8 days after transplantation. Immunoperoxidase stains for cells producing immunoglobulin (Ig) demonstrate a proliferation of Ig-containing immunoblasts in the splenic red pulp (RP) and peripheral periarterial sheath (PAS) within 2 days after transplantation. These immunoblasts differentiate into plasma cells that triple the RP volume by the time of rejection. By 14 days, the plasma cells are replaced by mitotically active large and small lymphocytes with no demonstrable cytoplasmic Ig. Splenic Ig production is followed by a venous vasculitis in the graft and by the appearance of circulating cytotoxic antibodies 5 days after grafting.
Three biological methods of prolonging cardiac graft survival were found to derange this sequence of immunological reactions at different stages. Enhancement by antigen and antibody pretreatment of the recipient elicited a premature production of Ig that subsided and was not reinitiated by cardiac transplantation. Transfer of suppression with thymocytes from enhanced cardiac recipients temporarily inhibited differentiation of splenic B cells into immunoblasts and plasma cells. T cell depletion by thymectomy, irradiation, and bone marrow reconstitution also decreased the plasma cell response, possibly by removing helper cells required to switch IgM production to IgG. These studies reemphasize the importance of Ig production in the complex interaction of immune reactions leading to acute rejection of organ transplants.