SUPPRESSION OF REAGINIC ANTIBODY-FORMATION .4. SUPPRESSION OF REAGINIC ANTIBODIES TO PENICILLIN IN MOUSE

  • 1 January 1976
    • journal article
    • research article
    • Vol. 117  (3) , 927-934
Abstract
Reaginic antibodies to the benzylpenicilloyl determinant (BPO) and ovalbumin (OA) were induced readily in B6D2F1 mice by a single i.p. injection of 1 or 10 .mu.g 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 .gamma.-globulins (M.gamma.G), i.e., BPO2-M.gamma.G, BPO11-M.gamma.G or BPO12-M.gamma.G, resulted in complete and specific suppression of the induction of the anti-BPO reaginic antibody response without affecting the level of reaginic antibodies to OA. Further study of the effect of epitope density on the immunologic properties of BPOx-M.gamma.G revealed the following: the lightly haptenated conjugates, BPO1-M.gamma.G and BPO2,9-M.gamma.G, were not immunosuppressive; the conjugates, BPO4.3-M.gamma.G and BPO19-M.gamma.G, were partially tolerogenic; and the heavily haptenated conjugate, BPO31-M.gamma.G, was nontolerogenic. The ongoing anti-BPO response in sensitized mice was readily abrogated by 4 daily or 4 weekly injections of BPO2-M.gamma.G. The immunosuppressive effect of BPO12-M.gamma.G conjugates was dose dependent, complete suppression being achieved with 200 .mu.g 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 administration of the immunizing antigen under conditions expected to yield a secondary IgE [immunoglobulin E] response. With special precautions to prevent anaphylactic shock, treatment of penicillin-sensitive individuals with polyvalent conjugates of an appropriate number of BPO groups per human .gamma.-globulin molecule would probably constitute a rational immunotherapeutic procedure for the abrogation of the allergic response to BPO.