Reactivity of Mast-Cell-Bound IgE Idiotypes with Anti-Idiotypic Antibody: Mediator Release or Inhibition of Antigen-Induced Mediator Release?

Abstract

When anti-idiotypic antibodies specific for idiotopes on IgE antibodies react with mast-cell-bound IgE antibody, the reaction may be expected to lead either to mediator release or to inhibition of allergen-induced release. This study was carried out to determine which would occur. Anti-idiotype antiserum (anti-Ids) was raised in syngeneic mice by immunisation with affinity-purified DNP-specific mouse monoclonal IgE. Sera from these immunised mice and from a similarly immunised rabbit inhibited the binding of the monoclonal IgE to radio-iodinated dinitrophenylated (DNP) ovalbumin, whereas a high concentration of affinity-purified rabbit antimouse epsilon-chain-specific antibody was unable to inhibit even though it was shown to bind to the monoclonal IgE. The mouse anti-Ids did not give a positive passive cutaneous anaphylactic reaction in rats sensitised with high-titre grass-pollen-specific IgE-containing antiserum, whereas it gave a positive result in rats sensitised with the DNP-specific monoclonal IgE. Rabbit antimonoclonal antiserum and rabbit anti-epsilon-chain antibody both gave positive results in these two assays. The results indicated that anti-idiotypic antibodies specific for idiotopes on IgE antibody can react and release mediators from IgE-sensitised mast cells. The significance of this in view of the increased levels of anti-idiotypes that can occur during immunotherapy is discussed.