The production and regulation of IgE by the immune system

The production of IgE and its clearance from the blood are tightly regulated, which results in transient IgE antibody responses and the maintenance of low steady-state levels of IgE.IgE can be generated by a direct class-switch recombination pathway from Sμ to Sε, by a sequential class-switch pathway from Sμ to Sγ1 followed by Sε, as well as by a recently described alternative sequential class-switch pathway from Sγ1 to Sε, which then joins to Sμ. Additional work is needed to better understand the contribution of each class-switch pathway to IgE production in health and disease.Early IgE antibody responses arise from extrafollicular sources, whereas later IgE responses are derived from germinal centres. IgE germinal centre responses are transient, which may limit IgE production.IgE plasma cells that are derived from germinal centres are predisposed to be short-lived in contrast to IgG1 plasma cells that are derived from germinal centres, and are primarily long-lived.IgE memory responses can arise from both IgE memory B cells and IgG1 memory B cells, but the contribution of each memory B cell subset to total IgE memory responses remains to be clarified.The high-affinity Fc receptor for IgE (FcεRI) on dendritic cells and macrophages, but not on mast cells or basophils, contributes to the clearance of serum IgE. By contrast, the low-affinity Fc receptor for IgE (FcεRII; also known as CD23) on B cells does not contribute to the clearance of serum IgE, but modulates total serum IgE levels by providing a sink that binds a substantial portion of the total IgE pool.A better understanding of IgE biology may lead to new approaches to treat IgE-driven allergic diseases such as asthma, allergic rhinitis and atopic dermatitis.