The biology of IgE: The generation of high-affinity IgE antibodies

B cells can undergo affinity maturation through the process of somatic hypermutation (SHM) followed by selection for high-affinity variants. Affinity maturation occurs in germinal centers (GC) and requires T-B cell cooperation. Extra GC B-cell responses are associated with the production of low-affinity antibodies. B cells producing high-affinity IgE during T-dependent responses are not directly selected in GC but are produced by the sequential switching of GC-selected high-affinity IgG-producing B cells. In contrast, natural low-affinity IgE can be generated without cognate T-B cell interactions in lymphopenic conditions. Low- and high-affinity IgE may differentially affect mast cell survival and degranulation and thus determine whether mast cells contribute to a beneficial or pathogenic environment.