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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2868-2869.
IgE-induced signaling: only the weak surviveThe dogma stating that the binding of immunoglobulin E (IgE) to its receptor (Fc RI) on mast cells is simply a passive presensitization step that requires subsequent cross-linking with multivalent antigen (Ag) to elicit or biologic effects was first challenged when it was shown that IgE alone could increase the cell surface expression of FcRI.1,2 Then, in 2001, 2 groups showed that IgE alone could enhance the survival of cytokine-deprived, bone marrow–derived mast cells (BMMCs).3,4 However, they disagreed on how. Kalesnikoff et al,3 using the highly potent SPE-7 IgE, proposed that IgE prolonged survival via intracellular signaling that led to the maintenance of Bcl-XL levels and the production of autocrine-acting cytokines. They also showed that IgE alone stimulated more prolonged Erk phosphorylation and higher levels of inflammatory cytokines than IgE(+Ag) and proposed that this might explain why IgE could induce survival while IgE(+Ag) could not. Asai et al,4 using the less potent Liu IgE, did not observe any IgE-induced signaling and proposed a signaling-independent mechanism for IgE-induced survival. However, a more recent paper by the latter group5 confirmed that signaling was essential since IgE-induced survival required the tyrosine kinase Syk, regardless of the IgE used.
Of the IgEs tested to date, SPE-7 is by far the most potent at inducing BMMC signaling/survival, and some investigators have been reluctant to extrapolate results obtained with this potentially "oddball" IgE to other IgEs because SPE-7 was recently shown to exist in 2 interconvertible conformations in the absence of Ag: one capable of binding to its hapten (dinitrophenol [DNP]) and the other to an unrelated protein.6 How common this isomerism is amongst IgEs is not yet known. Countering this argument, other IgEs have been shown to induce BMMC survival in vitro4,5 and to increase mast cell numbers in vivo.5
The Fc
In this issue of Blood, Yamasaki et al (page 3093) have circumvented the controversy surrounding SPE-7 by exploiting their finding that the Taken together with the work of Kalesnikoff et al3 and Kitaura et al,5 it is likely that certain highly potent IgEs are capable in vivo of increasing mast cell survival and inflammatory cytokine production via sustained Erk phosphorylation and that the severity of allergic disorders in some people may be due to the production of these IgEs.
References
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| Copyright © 2004 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
chain that binds IgE, a 
chain that amplifies the IgE-induced signal, and 2 
chains that transduce the signal. The 