The role of a functionally distinct IgM anti-type III pneumococcal polysaccharide (SIII) in low-dose paralysis to SIII in mice.
Prior treatment (priming) with a weakly immunogenic dose of Type III 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-IgM anti-SIII antibodies were present. Comparable inhibiton of the direct anti-SIII PFC response was observed when Concanavalin A (Con A) or NCF-IgM anti-SIII serum was administered with SIII antigen. That Con A and NCF-IgM anti-SIII together did not produce additive suppression was attributed to the adsorption of NCF-IgM 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-IgM or IgA anti-SIII antibodies and indicated that each of the antibodies was specific for the same SIII-determinant. Evidence is presented to show that low-dose paralysis in the CF-IgM response to SIII is not mediated by suppressor T cells but can be attributed to highly avid NCF-IgM 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 SIII is the result of an immunobiological function of highly avid NCF-IgM anti-SIII antibodies which not only confer resistance against capsulated pneumococci but preferentially bind soluble SIII-antigen to reduce its immunogenicity and thereby protect specific CF-IgM positive B cells from being rendered tolerant by direct contact with higher doses of SIII antigen.
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D003168:Complement Fixation Tests; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006462:Hemolytic Plaque Technique; D007106:Immune Sera / Q000276:immunology; D007108:Immune Tolerance; D007116:Immunization, Passive; D007075:Immunoglobulin M / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007106:Immune Sera; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial; C026604:pneumococcal polysaccharide, type III; D003208:Concanavalin A