IgE regulation of mast cell survival and function.

Traditionally, it is thought that IgE binding to mast cells via the high-affinity receptor (FcepsilonRI) is simply a passive 'sensitization' step prior to activation by receptor aggregation or cross-linking with multivalent antigen or other cross-linking agents. However, in addition to receptor up-regulation, recent studies have shown that monomeric IgE can induce survival and other activation events including increased histamine content, degranulation, leukotriene release, receptor internalization, adhesion, migration and DNA synthesis. Various IgE molecules exhibit a vast spectrum of heterogeneity: the highly cytokinergic (HC) group of IgEs at an extreme end of the spectrum can induce survival and other activation events very efficiently, whereas poorly cytokinergic (PC) IgEs at the other end can do so less efficiently. All the IgEs tested appear to be capable of inducing receptor aggregation with HC IgEs having a higher capacity to do so than PC IgEs. HC IgEs can promote the production and secretion of various cytokines including the one(s) that can sustain survival in an autocrine and paracrine mechanism. Consistent with receptor aggregation induced by monomeric IgE, other means of receptor aggregation, e.g. IgE+antigen and IgE+anti-IgE, can also induce survival and other events in unique ranges of stimulation intensity.