Idiotypic regulation by isologous monoclonal anti-idiotope antibodies

Abstract

The network hypothesis¹ proposes that internal antibody interactions are crucial in the regulation of the immune system. Thus, injection of minute amounts of anti-idiotypic antibodies (antibodies specific for a particular set of antigenic determinants (idiotopes) associated with the variable region of a particular antibody or set of antibodies) can enhance or suppress the production of the corresponding set of idiotopes (the idiotype) in subsequent antibody responses of the animal^2–5. We have recently shown that idiotope expression can be enhanced and suppressed by monoclonal anti-idiotope antibodies of the IgG1 class in concentrations approaching those of natural antibodies⁶. We now demonstrate that these regulatory effects are not due to differences in the constant parts of the injected antibody and antibodies of the IgG1 class in the recipient. Also, an IgG2a anti-idiotope antibody raised in C57BL/6 mice suppresses the expression of the corresponding idiotope in animals of the same strain when minute amounts are injected 2–8 weeks before the test immunization with antigen. These results indicate that antibody-mediated network interactions are physiologically important and suggest that the class of isologous anti-idiotypic antibodies may influence their regulatory properties. Finally, the enhancement and suppression of idiotope expression by IgG1 anti-idiotopes and the suppression by IgG2a is almost exclusively at the level of IgG but not IgM antibodies.