By HUGH AUCHINCLOSS , JR . , JEFFREY

The idiotype network hypothesis proposed by Jerne (1) has led to considerable interest in whether physiologic immunoregulation is accomplished by the interaction of receptor molecules and anti-receptors directed at unique idiotypic determinants. Another issue of importance, related to mechanistic questions, is whether exogenously administered anti-receptor antibodies might be used to manipulate immune responses. Because of the particular importance of major histocompatibility complex (MHC) 1 antigens in both transplantation and normal immunity, we have undertaken studies to determine whether antiidiotypic (anti°Id) reagents might be used to modify immune responses to these antigens. In the past, we have been unable to prepare anti-Id reagents against heterogeneous populations of anti-H-2 antibodies presumably because no single species of antibody was present in sufficient quantity to elicit a detectable anti-Id response. This problem has recently been overcome by using monoclonal anti-H-2 antibodies as the source of receptor material, and large quantities of xenogeneic anti-Id reagents have been generated by this means (2). However, again because of the heterogeneity of the antiH-2 responses, the question arises whether anti-Id generated against monoclonal antibodies would have anv effect on in vivo anti-H-2 humoral responses. We have recently reported (2, 3) the results of several studies demonstrating that treatment of mice in vivo with xenogeneic anti-Id induced the expression of molecules (Id') that share some of the idiotopes with the original Id but may or may not bind H-2 antigens. In addition, mice treated with xenogeneic anti-Id and subsequently grafted with skin bearing the original M H C antigen developed a significantly higher percentage of Id-positive alloantibodies than were detected in the alloantisera of untreated animals (3). These results led to the conclusion that treatment with anti-Id against monoclonal anti-H-2 antibodies can significantly alter B cell immune responses to M H C antigens (3-5). The present studies were undertaken in an at tempt to determine the mechanism by