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THE ROLE OF A FUNCTIONALLY DISTINCT IgM ANTI‐TYPE III PNEUMOCOCCAL POLYSACCHARIDE (SIII) IN LOW‐DOSE PARALYSIS TO SIII IN MICE
Author(s) -
Kearney R,
Andrews J,
Johnstone S
Publication year - 1986
Publication title -
australian journal of experimental biology and medical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0004-945X
DOI - 10.1038/icb.1986.3
Subject(s) - paralysis , medicine , surgery
Summary 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.