THE ROLE OF A FUNCTIONALLY DISTINCT IgM ANTI‐TYPE III PNEUMOCOCCAL POLYSACCHARIDE (SIII) IN LOW‐DOSE PARALYSIS TO SIII IN MICE

Abstract

Summary.Prior treatment (priming) with a weakly immunogenic dose of TVpe 111 pneumococcal polysaccharide (SIII) results in the development of an antigen-specific state of unresponsiveness termed low-dose paralysis which is believed to be mediated by suppressor T cells. The present findings show that the passive administration of functionally distinct non-complement-fixing (NCF) IgM anti-SIII antibodies either in monoclonal form or from protein-A absorbed immune serum could significantly suppress the direct plaque-forming cell (PFC) response to an immunogenic dose of SIII administered concurrently. The degree of suppression was comparable with that induced by low-dose paralysis. Low-dose paralysis was consistently induced in athymic (nude) mice 4 days, but not 3 days, after priming with a low dose of SIII, and was associated with the delayed appearance of NCF-IgM anti-SIII in the serum of athymic mice. In contrast, low-dose paralysis was readily induced in normal BALB/c mice 3 days after priming when NCF-lgM anti-SlU antibodies were present. Comparable inhibiton of the direct anti-SIH PFC response was observed when Concanavalin A (Con A) or NCF-lgM anti-Sill serum was administered with Sill antigen. That Con A and NCF-lgM anti-SIII together did not produce additive suppression was attributed to the adsorption of NCF-lgM anti-SIII antibodies to Con A. Complement-dependent single radial haemolysis mediated by CF hybrid igM/A or CF-IgM anti-SIII serum was blocked by monoclonal NCF-lgM or IgA anti-SIII antibodies and indicated that each of the antibodies was specific for the same Slll-determinant. Evidence is presented to show that low-dose paralysis in the CF-IgM response to Sill is not mediated by suppressor T cells but can be attributed to highly avid NCF-lgM anti-SIII antibodies, formed preferentially to low doses of SIII, being able to reduce the immunogenicity of SIII administered subsequently.We propose that low-dose paralysis to Sill is the result of an immunobiological function of highly avid NCF-lgM anti-SIII antibodies which not only confer resistance against capsulated pneumococci but preferentially bind soluble Slll-antigen to reduce its immunogenicity and thereby protect specific CF-lgM positive B cells from being rendered tolerant by direct contact with higher doses of Sill antigen.

Immunogenicity and immunochemistry ofStreptococcus pneumoniae capsular polysaccharides

“…When noncomplement-fixing anti-S3 antibodies are present, no high-dose tolerance is induced, and low-dose paralysis in the complement-fixing IgM response to $3 might not be mediated by Ts-cells, but can be attributed to highly avid non-complement-fixing IgM anti-S3-antibodies (Kearney et al 1986), formed preferentially at low doses of $3. The presence of specific serum anti-capsular antibodies does not necessarily imply immunity to pneumococci.…”