SELECTED ARTICLES FROM THE RECENT LITERATURE 2003

12/10/03

The central role of Fc epsilon R1 in allergy

Summary
It has been known for some time that the presence of the high affinity IgE receptor (Fc epsilon R1) on the surface of mast cells and basophils play a central role in initiating allergic inflammation by binding IgE antibodies. Following the exposure of allergic subjects to the offending allergen, the multivalent allergenic epitopes bind to adjacent IgE antibody molecules, pulling them together. This action pertubates the the inderlying Fc epsilon R1, leading subsequently to degranulation of mast cells/basophils with release of allergic mediators. It is believed that the effects of these mediator on different tissues results in the various manifestation of allergic reactions.

However, as reviewed by von Bubnoff et al of Friedrich-Wilhelms University in Bonn, Germany, the Fc epsilon R1 is expressed eon other cells besides mast cells and basophils. In recent years, it has been found that Fc epsilon R1 is expressed on the surface of antigen-presenting cells such as dendritic cells (DC) of atopics but generally not of non-atopics. These Fc epsilon R1 on DC also bind IgE. Following exposure to offending allergens, the DC do not degranulate. Rather, signal transduction pathways are activated leading to the expression of genes for inflammatory cytokines. Furthermore, the binding of allergenic epitopes to the IgE on the surface of DC acts to focus and enhance allergen presentation by these DC to T lymphocytes in an IgE-dependent manner. Thus, allergen-IgE interaction may lead to greater sensitization of the host as well as initiation of an allergic reaction.

Reference
Clin Exp Dermatol 2003; 28:184-7

Editor's Comments
I feel that the findings reviewed above are among the most exciting and potentially important recent developments in our understanding about the function of IgE antibodies. For years it was thought that IgE bound only to 2 cell types - mast cells and basophils. The recent findings that the Fc epsilon R1 is expressed on the DC of atopics adds additional concepts to the role of IgE antibodies.

One can ask why the Fc epsilon is expressed on the DC of atopics but not non-atopics. A very recent report by the authors listed above (J Clin Inv 2003;111:1047-56) indicates that such surface expression of Fc epsilon R1 is dependent on the amount of gamma chain of this receptor which is expressed in the cytoplasm This gamma chain expression appears to be down regulated in non-atopics. Also, extracellular IgE levels appear to stimulate Fc epsilon R1 expression of DC. Thus, one gets a positive feedback stimulation of Fc epsilon R1 expression once more IgE is synthesized. This relationship could also explain why Fc epsilon R1 surface expression is decreased following anti-IgE antibody therapy which reduces the levels of free IgE in the plasma.

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