Studies on immunological paralysis IV. The relative contributions of continuous antibody neutralization and central inhibition to paralysis with type III pneumococcal polysaccharide

Abstract

High-zone tolerance to type III pneumococcal polysaccharide (SIII) in CBA mice is demonstrable by complete inhibition of the direct plaque-forming cell (PFC) response in the spleen. The serum antibody which protects mice against pneumococcal infection and agglutinates SIII-sensitized mouse erythrocytes is not detectable following injection of amounts of antigen one order of magnitude lower. Evidence is presented that this is attributable to continuous peripheral neutralization of antibody by recirculating, non-degradable antigen. This zone of 'pseudo-paralysis' masks an immune response which, at the cellular level, is as intense as that induced by sheep erythrocytes. Tolerance can be lost spontaneously after many weeks and be succeeded by a strong immune response, but secreted antibody can again be neutralized by the presence of antigen in serum. Raised numbers of antigen-binding cells (rosettes) are detectable in fully tolerant (PFC-suppressed) animals. Serum anti-SIII activity can be detected in 'pseudo-paralysed' mice by haemagglutination, or preferably by haemolysis, of heavily-sensitized sheep erythrocytes. Evidence is presented that this represents the same IgM as is synthesized in immunized, protected mice, but which is here partially neutralized by co-existence with serum antigen. Only direct PFC's were detectable in response to purified SIII and the characteristics of their specific neutralization implied that IgM of essentially similar avidity was formed in response to all antigen doses. Partial neutralization of IgM by SIII is discussed in relation to differences in availability or affinity of combining sites on macroglobulin.