Intrinsic and extrinsic regulation of IgE B cell responses

Stringent regulation of IgE antibody production is critical for constraining allergic responses. This review discusses recent advances in understanding cell-intrinsic and extrinsic mechanisms that regulate the genesis and fate of IgE B cells. B cell-intrinsic regulation of IgE is orchestrated by the IgE B Cell Receptor (BCR). Through its antigen-independent signaling and low surface expression, the IgE BCR drives IgE B cells to differentiate into short-lived plasma cells and/or undergo apoptosis, restricting IgE-expressing cells from entering long-lived compartments. The pivotal extrinsic regulators of IgE responses are T follicular helper cells (T-FH). T-FH produce IL-4 and IL-21, which, respectively, are the major activating and inhibitory cytokines for IgE class-switching. Other newly identified T follicular subsets also contribute to IgE regulation. Although IgE responses are normally constrained, recent studies suggest that specific conditions can induce the formation of IgE responses with enhanced affinity or longevity, effectively 'breaking the rules' of IgE regulation.

Automated summary

Stringent regulation of IgE antibody production is crucial in constraining allergic responses. Both cell-intrinsic and extrinsic mechanisms play important roles in regulating the genesis and fate of IgE B cells, with IgE B Cell Receptor and T follicular helper cells being key players. Various cytokines produced by T-FH, such as IL-4 and IL-21, are essential in activating or inhibiting IgE class-switching. Recent studies have also found conditions that disrupt the normal constraints on IgE responses, leading to enhanced or prolonged IgE responses.