REGULATION OF IGE SYNTHESIS IN HUMANS

At the present time, in no other system are the signals required for i sotype switching better understood than in the IgE system. IgE switchi ng is therefore becoming a general model for ''directed'' isotype swit ching in mice and humans. The study of IgE regulation has proposed a p aradigm 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 respons ible for the choice of the isotype. The second signal is typically del ivered 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, stres sing in particular the cross-talk between signals, and the mechanisms responsible for IgE amplification.