Cytotoxic versus immunoblocking effects of specific alloantibodies: effects of IgM, IgG, and IgG2 on rat kidney allograft survival.
Passively introduced IgM alloantibodies of antidonor specificity regularly led to decreased kidney allograft survival times, whereas IgG alloantibodies from the same hyperimmune sera had a specific immunoblocking effect that promoted prolonged allograft survival. These strikingly opposite effects as a function of antibody isotype occurred across both strong H-1 (Ag-B) and moderate non-H-1 histocompatibility barriers. However, IgM and IgG directed against non-H-1 specificities were far more effective, respectively, in either curtailing or prolonging renal allograft survival. In the Fischer to Lewis strain combination, this was reflected in a 4-fold diminution in median survival time of IgM-treated recipients from 115 to 31 days, in contrast to indefinitely prolonged survival of IgG-treated recipients (greater than 350 days). Purified IgG2 alloantibodies proved as effective as the whole IgG fraction in passively promoting long-term renal allograft survival across a strong H-1 barrier. Conflicting data from other sources is evaluated. Possible mechanisms of specific immunoregulation are briefly discussed in relation to antibody properties of specificity, idiotype, class-subclass, and avidity-affinity.
D000818:Animals; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D003601:Cytotoxicity Tests, Immunologic; D006085:Graft Survival; D007112:Immunity, Maternally-Acquired; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew
D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies