Tolerance induction as an index of age-related changes

Tolerance to rabbit gamma globulin RGG) can be induced in newborn or three week old mice of all strains tested. In six week old SJL or NZB mice there is marked resistance against tolerance induction to RGG. This resistance increases with increasing age and is completed by the age of 12 weeks. Resistance to tolerance can be observed in 3 week old SJL animals when human IgG3 but not when human IgG1 or RGG is employed as tolerogen. Using IgG3, resistance to tolerance induction can be demonstrated in 28-34 week old A/J, C57BL/6J and DBA1/J mice. Thus resistance to tolerance induction seems to be a concomitant of aging; SJL and NZB differ from other strains only by the age at which this change is apparent. By the 6th week of age, SJL and NZB mice develop marked resistance to tolerance induction with RGG, and so do hybrids between these two strains; there is no complementation with respect to resistance against tolerance induction. Aggregate-freed iodinated rabbit gamma globulin (125I-RGG) but not mouse immunoglobulin is eliminated much more rapidly from the body of normal 6 week old SJL and NZB mice than from the body of hybrids. Complementation in the hybrids might occur and prevent a response to small quantities of aggregate-freed RGG.