Domain-Specific Anti-IgE Antibodies Interfere with IgE Binding to FcεRII

Human anti-IgE autoantibodies have been identified and implicated in the regulation of IgE-mediated reactions and IgE synthesis. In order to study the potential regulatory role of anti-IgE antibodies on IgE binding to the FceRII we used a panel of IgE-specific monoclonal antibodies that were mapped by Western blotting against a series of recombinant e domain peptides. Antibodies specific for all e domains were detected except those against CeHl. Using a competitive inhibition cell-binding assay on FceRII + 8866 cells, we identified two major patterns of anti-IgE activity. Antibodies specific for the CeH3 domain removed IgE whereas those specific for the CeH2 domain enhanced IgE binding to the FceRII. The anti-CeH2 antibodies, in contrast to the anti-CeFD antibodies, could not dissociate cell-bound IgE from the FceRII. Using preformed immune complexes of IgE and anti-IgE antibodies, it was clear that the anti-CeH2 antibodies bound more IgE to the FceRII by addition of immune complexes to the cell surface. Our results suggest that the opposing actions of either inhibition or enhancement of IgE binding by anti-IgE antibodies are related to their e domain specificity.