Idiotype-specific tolerance: preferential alteration of idiotype expression after neonatal exposure to tolerogen.

The development of HOPC-8 idiotype-positive and HOPC-8 idiotype-negative B cell subpopulations involved in the immune response to a single PC antigen, has been monitored during normal differentiation and in situations where neonatal tolerance had been induced. It was found that H8 id+ and H8 id- anti-PC antibody-secreting cells appeared at approximately the same time in ontogeny and these late maturing subsets constituted equal fractions of the immune response in CBA/CaJ X BALB/c F1 (JBF1) mice. However, when JBF1 mice were injected at birth with graded doses of PC-FGG, responses obtained in 4-week-old mice were predominantly of the H8 id. This PC-specific, idiotype-restricted, unresponsive state was stable upon adoptive transfer. Specific depletion of Thy-1.2-positive cells and in vitro "mixing" experiments involving combined ratios of tolerant and nontolerant spleen cells suggest that the unresponsive state measured 4 weeks after tolerogen administration does not involve suppressor cells. It would appear that intrinsic differences between these idiotypically defined B cell subsets account for the observed differential susceptibility to tolerance induction among PC-responsive B cells.