Studies on immune tolerance to heat-aggregated human IgG in rabbits: its relevance to the production of rheumatoid factors.

Rabbits neonatally tolerized with native monomeric human IgG and subsequently immunized with heat-aggregated human IgG emulsified in Freund's complete adjuvant, at a time when B cells but not T cells should have spontaneously recovered from tolerization, resulted in the production of an antibody resembling human rheumatoid factors directed against a single antigenic determinant in the Fc region of the IgG molecule. Rabbits immunized in an identical fashion after adult tolerization treatments failed to respond during the period corresponding to B-cell tolerance, but subsequently produced antibody or similar specificity to that produced by neonatally tolerized animals. These results indicate that no completely new antigenic determinants are created on heat aggregation of IgG, but there appears to be some potentiation of immunodominance of an already existing determinant. A possible mechanism for the production of rheumatoid factors in rheumatoid arthritis is suggested.