88.
In this study, immunization with a vaccine consisting of multiple F(abt’)
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 (Ab1t’) titer was higher than the titer of antibodies binding control antigens. The immunizing
F(abt’)
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 Ab1t’ was established by absorption and inhibition with antigen. Immunization with
antitetanus F(abt’)
2 (Ab1t’) fragments appears to have elicited naturally occurring autologous antitetanus toxoid antibody (Ab1t’) through an
idiotypic pathway. As predicted by network theory, anti-idiotype (Ab2) and antitetanus (Ab1t’) cycled reciprocally. Clonotypic
characterization of Ab1t’ using isoelectric focusing and affinity immunoblotting showed increases in Ab1t’ 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 Ab1t’ 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.
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