Date of Award

1983

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

BP vaccine is one of the adjuvants of choice for potentiating the IgE antibody response in rodents. In the present investigations administration of hapten (dinitrophenyl)-coupled Bordetella pertussis organisms (DNP-BP) failed to induce significant levels of anti-DNP IgE antibodies in CBA mice, regardless of the presence of an additional adjuvant {lcub}Al(OH)(,3){rcub}, while high levels of IgG antibodies were produced. The administration of DNP-BP to a number of inbred mouse strains, differing in H-2 genotype showed a clear segregation into low and high IgE responder Phenotypes. The low IgE responder status of CBA mice for DNP-BP, however, was not changed by conventional methods (irradiation and cyclophosphamide treatment).;Adoptive transfer of spleen cells from DNP-BP-treated donors into syngeneic recipients resulted in a delayed and weak but statistically significant suppression of anti-DNP IgE response following challenge with DNP-ovalbumin in alum, while transfer of purified T cells was ineffective.;Pretreatment of CBA mice with DNP-BP resulted in suppressed anti-DNP IgE but not IgG responses following conventional immunization with DNP-ovalbumin(alum). The suppression was hapten-specific and appeared relatively late. Despite the inability of CBA mice to produce IgE antibody in response to DNP-Bp, IgE B memory cells were generated. These cells mounted an IgE response only when provided with appropriately carrier-primed T helper cells.;Depletion of anti-DNP and anti-ovalbumin antibodies from the serum obtained from DNP-BP-treated DNP-ovalbumin-primed CBA mice, and subsequent administration of such serum into primed and nonprimed recipients resulted in DNP-specific suppression of the IgE response following immunization with DNP-ovalbumin. Treatment of adsorbed serum with anti-DNP antibodies inhibited the binding of ('125)I-DNP-BSA in a radioimmunoassay inhibition test, demonstrating anti-idiotypic activity. The anti-idiotypic activity was found associated with a serum fraction eluting with the bulk of immunoglobulins, from sephadex G-100.;Results strongly suggested the possibility that the hapten-specific, IgE-selective, suppression in CBA mice operates via auto-anti-idiotypic antibodies directed against one or more DNP-specific predominant idiotypes.

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