The use of hapten-polysaccharide conjugates for the induction of B-cell tolerance involving IgE responses. I. Preparation, characterization and specific tolerogenic activity of penicilloy l-substituted levans affecting IgE responses in normal and sensitized mice

Abstract

Benzyl penicillin was coupled directly to the hydroxylic groups of dextrans and levans, and indirectly to the amino groups of diaminopropyl-carboxymethyl-levans. Derivatives of both types were tested for their capacity to react with anti-penicilloyl antibodies, either in vitro (immunoprecipitation and its inhibition) or in vivo (inhibition of PCA reaction). Only derivatives coupled to diaminopropyl-carboxymethyl-levans were active by both criteria. High molecular weight penicilloyl-diaminopropyl-carboxymethyl-levans were tested for their immunogenicity (IgM response) and capacity to induce tolerance in the IgE component of anti-penicilloyl responses in DBA/2 and CBAT6T6 mice. The IgM response to the levan carrier was very much depressed by penicilloyl substitution of the levan, whilst that to the penicilloyl determinants was also very poor. These derivatives induced a state of IgE antibody tolerance when given before or after the induction of an allergic response with penicilloyl-ovalbumin. A higher degree of substitution was required for the induction of tolerance after immunization.

The tolerance induced was specific, since it did not affect IgE responses against ovalbumin and persisted for at least 3 months. Further challenges with penicilloyl-ovalbumin did not break the tolerant status.