Antibody synthesis induced by endogenous internal images.

Abstract

In this study, immunization with a vaccine consisting of multiple F(ab')2 fragments of affinity-purified antitetanus toxoid antibodies covalently bound to a carrier protein successfully induced antitetanus toxoid antibodies. Further studies showed that this vaccine preparation contained no biologically detectable tetanus antigen. The induced antitetanus antibody (Ab1') titer was higher than the titer of antibodies binding control antigens. The immunizing F(ab')2 preparation did not elicit a secondary antitetanus response from mice primed with tetanus toxoid and, hence, appeared free of tetanus epitopes. The specificity of Ab1' was established by absorption and inhibition with antigen. Immunization with antitetanus F(ab')2 (Ab1') fragments appears to have elicited naturally occurring autologous antitetanus toxoid antibody (Ab1') through an idiotypic pathway. As predicted by network theory, anti-idiotype (Ab2) and antitetanus (Ab1') cycled reciprocally. Clonotypic characterization of Ab1' using isoelectric focusing and affinity immunoblotting showed increases in Ab1' titer to be the result of increased synthesis by limited subsets of antitetanus toxoid B-cell clones and not increased synthesis by multiple clones, as is characteristic of antigen-driven Ab1 responses. Many Ab1 and Ab1' clonotypes had identical pIs, suggesting that they either share V region genes or are the product of the same B-cell clones. These findings indicate that immunization with polyclonal multivalent Ab1 preparations can trigger active synthesis of antibodies with the same specificity. The results provide further evidence for naturally occurring idiotypic cascades that could be exploited for studies of catalytic antibodies.