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.