The Regulation of IgE Synthesis

This chapter discusses the role of cells and cytokines, as well as the molecular mechanisms involved in human IgE synthesis. The central role of the CD40–CD40L pathway in IgE synthesis and, more generally, in isotype switching, was confirmed by the finding that defective switching in patients with X-linked hyper-IgM syndrome is due to mutations in CD40L that result in impaired CD40–CD40L interactions. The complexity in the interplay between T cells, B cells, and cytokines involved in IgE induction makes it difficult to unambiguously establish a chronology of the events leading to IgE synthesis. Nuclear factors specifically bind to relatively short DNA sequences, functionally defined as responsive elements. The general paradigm for promoters is that all slots for nuclear transcription factors need to be filled for a gene to fire. Secondary recombination, however, may represent a mechanism to prevent continued switching to downstream isotypes and to ensure isotype stabilization of switched B cells.