Lack of neonatal susceptibility to induction of tolerance by polysaccharide antigens

Abstract

Susceptibility to tolerance induction by polysaccharides during the neonatal period has been studied with the α-1.3 and α-1.6 glucosyl epitopes of dextran B 1355 in BALB/c mice and the β-2.6 fructosyl epitope of levan in CBA mice. Acquisition of responsiveness, as measured by plaque-forming cell (PFC) assays, is relatively late – taking more than 14 days to appear and 2–3 months to attain maturity in the case of α-1.6 glucosyl and β-2.6 fructosyl. The mice responded well to sheep red blood cells and 2,4-dinitrophenylated (DNP) keyhole limpet hemocyanin (KLH) by 14 days, but were refractory to another thymus-independent antigen DNP-Ficoll. Nonresponsiveness of 2-week-old spleen cells to the polysaccharides was stable on transfer and could not be attributed to suppressor cells. Despite this long post-natal phase of immaturity, no evidence was obtained of concomitant susceptibility to tolerance induction by dextran and levan. Response curves in mice injected at birth with weight-adjusted doses revealed similar or even higher “high-zone” thresholds to those tolerized at 3 months. Only partial α-1.3 glucosyl tolerance is inducible in adults but this was no greater after neonatal exposure, which led also to short-lived α-1.6 tolerance. Repeated injections of B 1355 and levan during the first 10 days was no more tolerogenic, and PFC appeared spontaneously with maturity in mice given these antigens neonatally. Thus, the recognized neonatal susceptibility to thymus-dependent antigens does not extend to these thymus-independent antigens. It is therefore considered that tolerance studied with polysaccharides has little relevance to the mechanism of self-tolerance acquired in the embryo and, in vivo, is determined by interaction with a relatively mature B cell rather than by “clonal abortion” of a tolerance-sensitive precursor stage.