Histamine Release Due to Bivalent Penicilloyl Haptens: The Relation of Activation and Desensitization of Basophils to Dynamic Aspects of Ligand Binding to Cell Surface Antibody

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Abstract
We study the time-dependent aspects of activation and desensitization of passively sensitized human basophils by a bivalent penicilloyl hapten, [BPO]2, in the presence or absence of a monovalent penicilloyl hapten, [BPO]1. Data presented in this and the preceding paper are found to be consistent with a simple kinetic model of the binding and cross-linking reaction between [BPO]1, [BPO]2, and cell surface IgE. It is shown that the rapid perturbation of cross-linked IgE by simple dilution or washing of cells or by addition of excess [BPO]1 causes re-equilibration of the rate of histamine release within a matter of seconds. This demonstrates that no stable antigenindependent “activated” state of basophils exists and that cross-linked antibody is necessary throughout the entire time course of histamine release. In addition, we show that desensitization requires the continuing presence of cross-linked antibody on the cell surface and that the rate of desensitization is a monotone increasing function of the number of cross-linked IgE molecules per cell. The rate of desensitization also appears to be a saturable function of the number of cross-linked IgE antibodies. In light of the kinetic model these data indicate that the binding and cross-linking reaction between [BPO]1, [BPO]2, and cell surface IgE approaches thermal equilibrium with a time constant on the order of 10 sec or less. This in turn implies that cyclic aggregates of [BPO]2 and IgE are unstable. Finally, since release and desensitization occur on a time scale of 100 sec or more, dynamic, as opposed to equilibrium, properties of the cross-linking reaction are unlikely to have any influence on [BPO]2-induced histamine release.