Triggers of IgE class switching and allergy development

The prevalence of immunoglobulin E (IgE)-mediated allergic diseases has been increasing for the last four decades. In this review determinants for an increased IgE synthesis are discussed on both an epidemiological and on an immunological level with special emphasis on the differentiation of the B cell to an IgE-producing plasma cell. Factors that favor an IgE immune response are low antigen doses and immunization via mucous membranes, but it is highly likely that other environmental factors besides exposure to the allergenic sources play a role. Important factors in the formation of the Thelper type 2 (Th2) T cell subset are the actions of thymic stromal lymphopoietin (TSLP) on dendritic cells and the OX40 ligand on CD4+ T cells. In order for a B lymphocyte to switch to IgE production it needs two signals provided by a Th2 cell in the form of the cytokines interleukin (IL-) 4/IL-13 and ligation of the CD40. In spite of a half-life of only a few days, there is evidence that the IgE response may last for years even without allergen stimulation. This is likely to be caused by long-lived IgE-producing plasma cells, and such cells may be difficult to target therapeutically thus emphasizing the need for more knowledge on preventable causes of IgE- and allergy development.