Age-dependent changes in isotype expression and down-regulation of C57BL/6 mice.

Age-related changes in antibody response and tolerance inducibility are polymorphic; in this paper isotype changes in ageing C57BL/6 mice are examined. Female C57BL/6 mice of various ages were immunized with either heat-aggregated RGG (a-RGG) or phosphorylcholine conjugate of RGG (PC-RGG); other animals of the same ages were given aggregate free RGG, followed by injections with either aggregated RGG or haptenated RGG. Sera from these four groups were analysed for antibody isotype. The data presented here indicate that age-related changes in isotype predominance and magnitude are different for different determinants. The capacity to be down-regulated appeared to undergo different age-related changes with different isotypes: there is split tolerance in isotypes. Age-dependent changes in T- and B-cell tolerance could be deduced by comparing responses of animals to hapten and to carrier determinants. In 5-week-old animals tolerance to hapten was more profound than tolerance to carrier. It was concluded that T-cell regulation dominated the response at this age. With advancing age, i.e. by 95 weeks, tolerance is observed in response to hapten but not in response to carrier determinants. We concluded that suppressor cells were induced by aggregate free RGG and affected the response of 'naive' but not of 'experienced' B cells.