The IgE Antibody Response
IgE is predominantly synthesized in perimucosal lymphoid tissues of the respiratory and gastrointestinal tract. In developing countries the main antigenic stimulus for IgE synthe-sis are parasites (particularly nematodes). Levels of circulating IgE considered as normal in a developing country with endemic parasitism are two to three orders of magnitude higher than in the western world. The vast majority of allergens, which are either ingested or inhaled, stimulate the same perimucosal tissues. In the perimucosal tissues only B lym-phocytes with membrane IgE will differentiate into IgE-producing plasma cells. Those IgE-carrying B cells are a only a small fraction of the total B cell population in the submu-cosa but are overrepresented in the perimucosal lymphoid tissues compared to other lym-phoid territories.
During the primary immune response to an allergen or a parasite, most of the IgE syn-thesized appears to be of low affinity. The changes occurring after a second exposure in-clude the synthesis of IgE of progressively higher affinity, probably as a consequence of somatic hypermutations. This may be the reason why allergic re-actions very seldom develop after the first exposure to an allergen. When a hypersensitiv-ity reaction appears to develop after what seems to be a first exposure to any given aller-gen, one must consider the possibility of cross-reaction between a substance to which the individual was previously sensitized and the substance that elicits the allergic reaction. Such cross-reactions are usually due to molecular mimicry and can be quite unpredictable.
Repeated exposures to parasites or allergens will stimulate the differentiation of memory cells and the proportion of circulating high-affinity antigen-specific IgE will also increase with repeated exposures. In patients suffering from severe pollen allergies, anti-gen-specific IgE may constitute up to 50% of the total IgE.