174 Anti - Idiotypes in Nzb

The network theory of the immune system proposes that idiotype-anti-idiotype interactions provide important immunoregulatory controls (1). In many experimental systems, the passive administration of heterologous anti-idiotypic ant ibody has been shown to enhance (2) or suppress (3) immune responses. In addition, spontaneous auto-anti-idiotypic antibody has been detected after antigenic challenge (4), generally appearing coincident with a decline in antibody titer (5). These findings have suggested that network controls might similarly regulate the formation of pathological autoantibodies (6). Two recent studies support this hypothesis. In one, rabbit anti(anti-thyroglobulin) idiotype prevented spontaneous auto immune thyroid disease in Buffalo rats (7). In the other, anti-(anti-DNA)-idiotype was found in the serum of systemic lupus erythematosus (SLE) 1 patients when they were in remission (8). In the current work, we have investigated the SLE mouse strain NZB for anti(autoantibody)-idiotypic antibodies that might play an immunoregulatory role. With age, these mice spontaneously produce IgG anti-erythrocyte autoantibodies which mediate a severe Coombs-positive hemolytic anemia (9). The Fa hybrids of NZB and several normal strains are known to develop a milder hemolytic disease with lower levels of Coombs antibodies (10). We have found that some of these hybrids spontaneously produce high titers of anti-(anti-erythrocyte)-idiotype antibodies that specifically recognize the NZB Coombs idiotypes. This finding suggests that network idiotype-anti-idiotype control might play a protective role in suppressing autoant ibody formation in these animals.