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 (VH and VL) of IgE antibodies and target antigen. It is now feasible to investigate the molecular nature of VH 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 VH genes, with dominance of the small VH5 family, particularly the VH32 gene, has been found. This may implicate a B cell superantigen (superallergen) selectively driving the use of these genes. Second, VH5 genes in IgE are somatically mutated with clear hot spots of mutational activity. Mutational hotspots, which are a feature of the VH5 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.