Immunogenetics of human IgE

Immunoglobulin E plays a central role in mediating the pathology of allergic disease. Conversely, it is involved in the normal protective immune responses against parasite infection. Both these biological processes depend on interaction between the variable regions (V_H and V_L) of IgE antibodies and target antigen. It is now feasible to investigate the molecular nature of V_H regions used to encode IgE at the genetic level. Using this technology to analyze IgE in patients with asthma has revealed features which may have relevance for allergic disease. First, preferential choice of V_H genes, with dominance of the small V_H5 family, particularly the V_H32 gene, has been found. This may implicate a B cell superantigen (superallergen) selectively driving the use of these genes. Second, V_H5 genes in IgE are somatically mutated with clear hot spots of mutational activity. Mutational hotspots, which are a feature of the V_H5 gene, are supplemented in IgE by ongoing mutations which may be involved in affinity maturation. Third, a single B cell can switch to either IgE or IgG4, with both variants coexisting in blood. These findings may provide clues to the mechanism by which IgE is generated, and suggest options for therapeutic intervention.