Termination of Immunologic Tolerance in Mice by Antigen-Antibody Complexes. ∗

Abstract

Summary

Eisen and Karush(l) proposed a model for the extracellular control of immunity and tolerance based on the assumption that bimolecular antigen-antibody (AgAb) complexes stimulate antibody formation, while trimolecular Ag²Ab complexes induce immunologic tolerance because they are not taken up by the immunologically competent cells. The model predicts that it should be possible to initiate an immune response in cells from tolerant animals provided they are stimulated with the appropriate AgAb complexes. Newborn NIH white mice were made tolerant to human serum albumin (HSA). At 7 weeks of age, single-cell suspensions were prepared from the individual spleens of the tolerant animals and exposed in vitro to HSA and rabbit anti-HSA mixed in 1:1 or 10:1 molecular ratios, to HSA only, or to a salt solution. The spleen cells were then injected intraperitoneally in the same mouse from which they had been removed. After challenge with HSA in incomplete Freund's adjuvant, the mice were tested by the tanned-cell hemagglutination procedure and by measurement of the rate of HSA elimination. Within 2 weeks following challenge, tolerance was broken in 55% of the mice whose cells had been exposed to AgAb complexes. In contrast, almost 90% of the mice whose cells had been treated with antigen only or with saline remained tolerant.