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 (14)C-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 (14)C-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 (14)C-SIII excluded reticuloendothelial blockade. The application of parabiosis followed by separation excluded the presence of a phagocytosis-resistant fraction of (14)C-SIII. Continual leakage of phagocytosed (14)C-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 (14)C-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 (14)C-SIII levels rather than tissue depots largely determined antibody neutralization. The contribution of this mechanism to polysaccharide paralysis is discussed.