Immunoglobulin class switch recombination ( 9, 17) is the mechanism whereby activated B cells “switch” their constant region while maintaining their antigen-binding domain, resulting in the production of IgG, IgA, and IgE antibodies ( Figure 2).
Both plasma cells of higher affinity ( 12), and memory B cells of broad affinity range ( 13– 16) emerge from the germinal center reaction. This process occurs in germinal centers and involves the somatic mutation of V(D)J genes followed by selection of higher affinity B cell clones through interaction with both antigen-loaded follicular dendritic cells (FDC) and T follicular helper cells (Tfh) ( 8– 11). Affinity maturation is the mechanism by which B cells improve the recognition of their cognate antigen by refining the affinity of their B cell receptor (BCR). The classical humoral memory of IgM, IgGs and IgA antibodies is mediated by a two-pronged mechanism ( 5): non-dividing quiescent memory B cells that can be quickly reactivated, and long-lived plasma cells ( 6, 7) that constantly secrete antibodies during their lifespan ( Figure 1 and Table 1).Īffinity maturation and class switch recombination of antibody genes are the central processes in the establishment of effective B cell memory. Despite the importance of IgE in allergic pathology, very little is known about the origin of human IgE B cells and the mechanisms of humoral IgE memory. Possibly as a consequence of this dual beneficial and pathogenic potential, IgE production has been evolutionary conserved but is strongly regulated. IgE antibodies also have protective functions against parasite infections and toxins ( 3, 4). While a high titer of serum IgE has long been considered the cardinal marker of atopy, IgE-producing cells are extremely rare in humans and mice, suggesting that IgE production is strongly regulated. Furthermore, the beneficial effect of anti-IgE treatment on allergic asthma and other chronic allergic diseases validated IgE as a therapeutic target ( 2). Given the increasing prevalence of allergic reactions and allergic diseases, the study of human IgE cells becomes extremely important. IgE antibodies mediate allergic diseases through their ability to bind to high-affinity receptors on mast cells and induce degranulation upon allergen crosslinking ( 1). General Mechanisms of Humoral Memory in Mice and Humans As will be discussed in depth in this review, the IgE memory response has unique features that distinguish it from classical B cell memory. There has been a dramatic increase in the incidence of allergic diseases in recent decades and this has provided the impetus to study the nature of IgE antibody responses. IgE responses have evolved for protection against helminth parasites infections and against toxins, but IgE is also a potent mediator of allergic diseases. Developing effective immunological memory is essential for protection against pathogens, and is the basis of successful vaccinations. Humoral immunity is maintained by long-lived plasma cells that secrete antigen-specific antibodies, and memory B cells that rapidly respond to antigen re-exposure by generating new plasma cells and memory B cells.
The long-term effectiveness of antibody responses relies on the development of humoral immune memory. 3Department of Cell Biology, New York University School of Medicine, New York, NY, United States.2Sackler Institute of Graduate Biomedical Sciences, New York University, New York, NY, United States.1Division of Pulmonary, Critical Care and Sleep Medicine, Laboratory of Allergy and Inflammation, Department of Medicine, New York University, New York, NY, United States.
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