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Suppression of Reaginic Antibody Formation¹

IV. Suppression of Reaginic Antibodies to Penicillin in the Mouse

MRC Group for Allergy Research, Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0W3

Abstract

Reaginic antibodies to the benzylpenicilloyl determinant (BPO) and ovalbumin (OA) were induced readily in B₆D₂F₁ mice by a single i.p. injection of either 1 or 10 µg of BPO₄-OA suspended with 1 mg of Al(OH)₃ in 0.5 ml of saline. Administration of conjugates consisting of the hapten coupled to the isologous, nonimmunogenic murine -globulins (MG), i.e., BPO₉-MG, BPO₁₁-MG, or BPO₁₂-MG, resulted in complete and specific suppression of the induction of the anti-BPO reaginic antibody response without affecting, however, the level of reaginic antibodies to OA. Further study of the effect of epitope density on the immunologic properties of BPO_x-MG revealed that a) the lightly haptenated conjugates, BPO₁-MG and BPO_2.9-MG, were not immunosuppressive, b) the conjugates, BPO_4.3-MG and BPO₁₉-MG, were partially tolerogenic, and c) the heavily haptenated conjugate, BPO₃₁-MG, was nontolerogenic. Moreover, most importantly, the ongoing anti-BPO response in sensitized mice was readily abrogated by either four daily or four weekly injections of BPO₉-MG. The immunosuppressive effect of BPO₁₂-MG conjugates was dose dependent, complete suppression being achieved with 200 µg of the tolerogen. The unresponsiveness to BPO of spleen cells from immunosuppressed donors was also maintained in adoptive cell transfer experiments in spite of the additional administrationof the immunizing antigen under conditions expected to yield a secondary IgE response. Hence, it is suggested that, with special precautions to prevent unleashing an anaphylactic shock, treatment of penicillin-sensitive individuals with polyvalent conjugates of an appropriate number of BPO groups per human -globulin molecule would constitute a rational immunotherapeutic procedure for the abrogation of the allergic response to BPO.

Footnotes

¹ This investigation was supported by grants from the Medical Research Council of Canada, Ottawa (Ontario).

² Holder of a scholarship from the Medical Research Council of Canada.