Can experimental B cell tolerance serve as a model for self tolerance?

Abstract

We have examined the abilities of the mature and immature immune systems to discriminate between tolerogenic and nontolerogenic forms of a hapten-carrier conjugate; both forms are multivalent nonimmunogenic polymers of the same molecular weight, and have the same avidity for free, hapten-specific antibody and hapten-binding B cells. Hapten-specific tolerance was induced in adult B cells by nonimmunogenic dinitrophenylated carboxymethyl cellulose or methyl cellulose. Oxidation and subsequent reduction of the vicinal hydroxyl groups of both carriers aborgated tolerogenicity, although they remained nonimmunogenic. This chemical modification did not affect the carrier's molecular weight, and it did not reduce the binding avidity of their hapten derivatives to hapten-specific antibody or to antigen-binding B cells. The same experiments, when carried out in either neonatal mice or mice that had been lethally irradiated and given the above compounds during treatment with 13-day-old fetal liver cells, invariably yielded the same results. Like adult mice, these immunologically immature animals were capable of distinguishing between the tolerogenic and the nontolerogenic form of each antigen. It has also been shown (C. A. Waters et al., in preparation) that neonatally induced tolerance to TNP-HGG is irreversible, whereas tolerance to TNP-BSA is reversible by challenge with TNP-LPS. These results are in conflict with the clonal abortion hypothesis.