Regulation of IgE synthesis in humans

At the present time, in no other system are the signals required for isotype switching better understood than in the IgE system. IgE switching is therefore becoming a general model for 'directed' isotype switching in mice and humans. The study of IgE regulation has proposed a paradigm of general importance for immunology in the nineties, namely, the requirement for at least two signals in order to trigger the final event, in this case DNA switch recombination to the IgE isotype. The first signal is delivered by a cytokine, IL-4 or IL-13, and is responsible for the choice of the isotype. The second signal is typically delivered upon engagement of CD40 on B cells by the CD40 ligand expressed on T cells, and results in switching and production of IgE. We shall herein discuss the two-signal model for IgE switching in detail, stressing in particular the cross-talk between signals, and the mechanisms responsible for IgE amplification.