Fc Receptors for IgE and Interleukin-4 Induced IgE and IgG4 Secretion

IgE binds to two types of Fc receptors, called Fc∈R1 (or high-affinity Fc∈R) and Fc∈R2 (or low-affinity Fc∈R). The Fc∈R1 is composed of four polypeptide chains, one α, one β, and two γ chains. The α chain contains the IgE binding site and is a member of the immunoglobulin supergene family. The Fc∈R2, also called CD23, consists of one polypeptide chain which shows homology to animal lectin receptors. Fc∈R1 are expressed on mast cells and basophils. Crosslinking of the Fc∈R1 induces immediate release of mediators of inflammation such as histamine and leukotrienes and delayed secretion of interleukins 4, 5, and 6. Fc∈R2 are expressed on resting μδ+ B cells, monocytes/macrophages (MΦ), eosinophils, and platelets but rarely on T cells. Interleukin-4 up-regulates Fc∈R2 expression on B cells and MΦ. The functions of Fc∈R2 on the different cell types are not fully established and are controversial. Fc∈R2 on MΦ, eosinophils, and platelets mediate cytotoxicity to schistosomules, enhance phagocytosis, and induce the release of granule enzymes. However, MΦ from patients with atopic dermatitis expressing significantly more Fc∈R2 than MΦ from normals do not release more leukotriene C4, prostaglandin E2, or β-glucuronidase after incubation with aggregated IgE than normal monocytes. Furthermore, aggregated IgG1 is much more efficient than IgE in inducing mediator release from MΦ and IgG1 antibodies are not known to induce immediate-type hypersensitivity reactions. Therefore, definitive proof that Fc∈R2 are involved in the pathogenesis of allergic disorders is still lacking. IL-4 appears to play a central role in immediate-type hypersensitivity. It induces human B cells to secrete IgE and IgG4, Ig isotypes typical for antibodies to helminthic parasites and allergens. IL-4 stimulates mast cell growth and up-regulates Fc∈R2 expression. Interferon-γ and IL-2 inhibit the IL-4-induced IgG4 and IgE secretion. Whether the abnormally high IgE antibody production in atopic patients is the result of overproduction of IL-4 or deficient IFN-γ/IL-2 production is presently unknown