Regulation of IgE synthesis.

IgE is produced mainly by plasma cells in diffuse mucosal-associated lymphoid tissues. Its synthesis is the result of three sets of tightly-regulated processes: activation of antigen-specific B cells in lymph nodes, class-switch recombination to IgE and survival of Bϵ memory cells and plasma cells. Triggered by specific T lymphocytes that have migrated to regional lymph nodes, the switch to IgE within follicular areas of these nodes is driven by the interaction of the CD40 receptor with its ligand on activated T cells, acting together with IL-4 and IL-13, whereas TGF-β specifically blocks Cϵ germline transcription to keep the rate of IgE synthesis far lower than that of other immunoglobulin classes. Disproportionate maturation of dendritic cells exposed to non-replicating environmental antigens, promoting the differentiation of specific T cells into effectors that produce type 2 cytokines instead of inducing regulatory T cells, is essential for the initiation and maintenance of IgE responses beyond the sensitization phase. Feedback regulation via IgE receptors (e.g., FcϵRI) and inflammatory mediators compartmentalizes IgE synthesis in the mucosa by orchestrating the cooperation of dendritic cells, memory lymphocytes, and mast cells. [Copyright &y& Elsevier]