Regulation of the IgE isotype switch: new insights on cytokine signals and the functions of var epsilon germline transcripts

In allergic responses, B cells are driven to undergo an immunoglobulin isotype switch, shifting from IgM to IgE synthesis. This process involves the rearrangment of germline DNA in the immunoglobulin heavy-chain locus and is stimulated by cytokines (IL-4 and IL-13) and CD40 activation. It is now evident that cytokine-induced ‘germline’ var epsilon-RNA transcripts associate with DNA in the genomic switch region (Svar epsilon) to form DNA–RNA hybrid structures, which target nucleases in for deletional switch recombination. Alterations in cytokine production and signaling affect the efficiency of this process and are associated with inherited predisposition to allergy.