A model of cell activation and desensitization by surface immunoglobin: the case of histamine release from human basophils.
We present a model for the control of immunoglobulin E (IgE)-mediated histamine release from human basophils. We suggest that there is a calcium gating factor which interacts with crosslinked IgE to form a short-lived open calcium channel. After formation of the channel the activated gating factor rapidly decays to an inactive form. It is the loss of the active gating factor which causes the basophil to desensitize nonspecifically. We propose that the crosslinked IgE molecules are deactivated by a mechanism, such as endocytosis or shedding, which is independent of the mechanism which inactivates the calcium gating factor. This loss of functional IgE leads to specific desensitization. The mathematical formulation of the model explains the relationship of specific and nonspecific desensitization to the amount of specific IgE on the basophil surface; explains why there are two types of antigen excess inhibition; explains the relationship between antigen excess inhibition and desensitization; explains why, for a fixed antigen concentration, increasing the concentration of cell surface IgE increases histamine release until an optimal concentration is reached, then decreases histamine release; predicts the effects that changing the external calcium will have on the dose response curve; and predicts that increasing the amount of specific IgE on the cell surface will cause the dose response curve to undergo a transition from a curve with a single maximum to a curve with two maxima.
D001491:Basophils / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D003888:Desensitization, Immunologic; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D007473:Ion Channels; D008433:Mathematics; D008954:Models, Biological; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011961:Receptors, Fc / Q000378:metabolism
D007473:Ion Channels; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D007073:Immunoglobulin E; D002118:Calcium