Different Stabilities of the Structurally Related Receptors for IgE and IgG on the Cell Surface Are Determined by Length of the Stalk Region in Their α-Chains

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Abstract
A variant of the high affinity IgE receptor FcεRI, which is composed of α- and γ-chains without the β-chain, is expressed on human APC, such as dendritic cells, and has been suggested to facilitate Ag uptake through IgE and hence to facilitate Ag presentation to T cells. The level of FcεRI on these cells is correlated with the serum IgE concentration, suggesting IgE mediates the up-regulation of the αγ2-type FcεRI. The IgE-mediated FcεRI up-regulation on mast cells and basophils has been shown to enhance the ability of these cells to release chemical mediators and cytokines that are responsible for allergic inflammatory reactions. Here, to elucidate the mechanism controlling FcεRI expression, we compared two structurally related Ig receptors, human FcεRI and FcγRIIIA, which carry different α-chains but the same γ-chains. The half-life of FcεRI on the cell surface was short unless it bound IgE, whereas FcγRIIIA was stably expressed without IgG binding. Shuffling of the non Ig-binding portions of the FcεRIα and FcγRIIIAα chains revealed that the stalk region was critical in determining the difference in their stability and ligand-induced up-regulation. Unexpectedly, analyses with added or deleted amino acids in the stalk region strongly suggested that the length rather than the amino acid sequence of the stalk region was of major importance in determining the different stabilities of FcεRI and FcγRIIIA on the cell surface. This finding provides new insights into the mechanism regulating surface FcεRI expression.

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