[Cellular interactions of IgE: towards a new function for IgE]

The anaphylactic function of IgE has been intensively investigated. The Fc epsilon receptor on mast cells or basophils combines with the last two constant domains of the epsilon heavy chain. The Fc epsilon receptor is apparently a glycoprotein, monovalent and free in the plasma membrane. The interaction between the antigen (allergen) and the corresponding IgE antibody combined with the Fc epsilon receptor results in the aggregation of the receptors. Receptor dimerization suffices to trigger the cell. Compartments can be described in mast cells or basophils, the activity of which depends upon the number of formed receptor dimers on the corresponding membrane area. Beyond a threshold number of dimerized receptors, the cell compartment is triggered, which in the presence of Ca++ leads to the discharge of mast cell mediators, an increasing function of the dimer number. Excess receptor aggregation or the absence of aggregation (i.e. IgE-Ag2 complexes) deactivates the cell, which occurs more often in the absence of Ca++. Thus, IgE molecules play a passive role only in allowing the aggregation of the receptors which delivers the activating signal. But through the composition of IgE-antigen complexes bound to the receptors, IgE also modulates the cell function according two antagonistic reactions in permanent balance, i.e. activation or deactivation. IgE molecules are also involved in immediate type reactions in inducing the release of lysosomal enzymes from mononuclear phagocytes. But IgE antibody can also, when complexed with the antigen, trigger macrophage cytotoxicity for the corresponding target, which indicates a new function of IgE in the effector mechanisms of immunity of particular importance in immunity to schistosomes. A receptor for aggregated IgE has been characterized on the membrane of macrophages. The binding of IgE to its macrophage receptor triggers the cell, as shown by the resulting increase in cyclic GMP, calcium uptake and accelerated turn-over of lysosomal enzymes. A receptor for IgE has also been described on lymphoid cells, B cells, null cells and recently T cells, and the appearance of the receptor is modulated by IgE molecules themselves, suggesting a homeostatic role of IgE molecules. IgE appears thus to play various functions, the most dramatic being the triggering of anaphylactic reactions. But the role of IgE in activating mononuclear phagocytes or lymphoid cells might also prove to be of importance in immunity.