Studies on immunological paralysis. 3. Recirculation and antibody-neutralizing activity of 14C-labelled type 3 pneumococcal polysaccharide in paralysed mice

Abstract

Clearance of a paralysing dose of ¹⁴C-labelled type III pneumococcal polysaccharide from the circulation in CBA mice was found to be exponential for about 6 days, but slowed thereafter. A persisting `tail' of free immunogenic ¹⁴C-SIII remained at levels between 0·1–1%, even after 100 days. This was not prevented by active or passive immunization, although the latter promoted early clearance. The mechanism responsible for this heterogeneity of elimination was investigated. Normal clearance of colloidal carbon and a second dose of ¹⁴C-SIII excluded reticuloendothelial blockade. The application of parabiosis followed by separation excluded the presence of a phagocytosis-resistant fraction of ¹⁴C-SIII. Continual leakage of phagocytosed ¹⁴C-SIII into the circulation was implicated by its gradual reappearance after total elimination by anti-SIII, a procedure which could be repeated.

The ability of recirculating ¹⁴C-SIII to continuously neutralize antibody synthesis on a `treadmill' basis was investigated by parabiosis of paralysed to optimally-immunized mice. Serum antibody was eliminated throughout 6 weeks of union. The data implied that serum ¹⁴C-SIII levels rather than tissue depots largely determined antibody neutralization. The contribution of this mechanism to polysaccharide paralysis is discussed.