4.1 Role of IgE on mast and basophils responses.
Mast cells and basophils were identified in tissue and blood, respectively, by Ehrlich almost 200 years ago, and their function was anticipated during this period55 describes early findings by Ehrlich). However, the functional relationship between these cells was not described in detail until after the discovery of IgE. Follow-up experiments by T. and K. Ishizaka revealed that both cells were activated through the high-affinity IgE receptor in the presence of IgE. Allergen-induced cross-linking of IgE bound to FcεRIs on the surface of mast cells or basophils induce aggregation of the receptor and intracellular signalling events56 that leads to Ca+-dependent release of preformed mediators and de novosynthesis and secretion of lipid mediators and cytokines (e.g. IL-4 and IL-13)57,58 (Figure 2). The concentration of serum IgE regulates the FcεRI surface expression on these effector cells, and this feedback mechanism can reduce the allergen concentration needed for activation59. Moreover, recent findings suggest that IgE’s glycosylation (sialylation) may be critical for the activation of mast cells in a mouse model of anaphylaxis based on IgE60. The essential role of IgE cross-linking that leads to activation of effector cells has obtained less attention but was described in detail for basophils by Christensen et al.61 and later similar observations were made for mast cells62. These studies confirmed that the concentration of allergen-specific IgE, IgE affinity and the ratio of allergen-specific to total IgE are the governing factors for the strength of effector cell release. The effect of specific to total IgE ratio and the observation that one high-affinity IgE in a mixture overrides the difference between high, medium, and low-affinity IgE may explain why correlations between concentrations of allergen-specific IgE and clinical symptoms has been difficult to establish63. Detailed studies with model antigens demonstrate that the spacing between the epitopes is critical64 and the number as well as relative positioning of IgE epitopes on allergens65,66 may also be critical for the ability to cross-link the receptors, which adds to the complexity of IgE-mediated effector cell activation.