Cross-linking of receptor-bound IgE to aggregates larger than dimers leads to rapid immobilization.
Controlled cross-linking of IgE-receptor complexes on the surface of rat basophilic leukemia cells and mast cells has allowed a comparison of the lateral mobility and cell triggering activity of monomers, dimers, and higher oligomers of receptors. Addition of a monoclonal anti-IgE(Fc) antibody to IgE-sensitized cells in stoichiometric amounts relative to IgE produces IgE-receptor dimers with high efficiency. These dimers are nearly as mobile as IgE-receptor monomers and trigger cellular degranulation poorly, but in the presence of 30% D2O, substantial immobilization of the dimers is seen and degranulation activity doubles. Addition of this monoclonal antibody in larger amounts results in the formation of larger oligomeric receptor clusters which are immobile and effectively trigger the cells. Thus, small receptor clusters that are active in stimulating degranulation are immobilized in a process that is not anticipated by simple hydrodynamic theories. Further experiments involving cross-linking of receptor-bound IgE by multivalent antigen demonstrate that immobilization of receptors occurs rapidly (less than 2 min) upon cross-linking and is fully and rapidly reversible by the addition of excess monovalent hapten. The rapidity and reversibility of the immobilization process are entirely consistent with the possibility that immobilization represents a recognition event between clustered receptors and cytoskeleton-associated components that plays an important role early in the cell triggering mechanism.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D003432:Cross-Linking Reagents; D004058:Diffusion; D005454:Fluorescence Polarization; D005455:Fluorescent Antibody Technique; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism*; D007938:Leukemia; D046911:Macromolecular Substances; D008407:Mast Cells / Q000276:immunology*; D008560:Membrane Fluidity; D051381:Rats; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D012701:Serotonin / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D003432:Cross-Linking Reagents; D046911:Macromolecular Substances; D011961:Receptors, Fc; D017455:Receptors, IgE; D012701:Serotonin; D007073:Immunoglobulin E