Inhibition of IgE binding to mast cells and basophils by monoclonal antibodies to murine IgE.
In an attempt to identify the site on IgE which binds with high affinity to the Fc epsilon receptor (Fc epsilon R) on mast cells, we established monoclonal anti-IgE antibodies (mAb) by fusion of myeloma cells with rat splenocytes immunized with purified murine IgE mAb. Six individual mAb were found to react with various IgE mAb of different specificities and not with immunoglobulins of other classes. Three different clusters of epitopes on the Fc epsilon portion could be detected by antibody competition studies. These antigenic determinants were expressed on the Fc epsilon portion and required the two heavy chains in their native conformation. Two groups of mAb and their Fab' fragments completely inhibited the binding of 125I-labeled IgE to rat basophilic leukemia cells (RBL), and one mAb inhibited the specific IgE binding only partially (55-65%). Likewise, the Fab' fragments of the purified mAb inhibited the antigen-mediated, IgE-dependent, serotonin release of RBL cells. These in vitro findings were confirmed by in vivo experiments, which demonstrated that the anti-IgE mAb could specifically block passive cutaneous anaphylaxis reaction when injected i.d., before challenging with the antigen. The differences in blocking reactivity of the various anti-IgE mAb are discussed in view of heterogeneity in the IgE-Fc epsilon R interaction.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal; D001491:Basophils / Q000378:metabolism*; D000939:Epitopes; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007942:Leukemia, Experimental / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D012701:Serotonin; D007073:Immunoglobulin E