REGULATION OF IGE SYNTHESIS BY CD23 CD21 INTERACTION/

At least two cell-derived signals have been shown to be necessary for the induction of immunoglobulin isotype switching in B cells. The firs t signal is given by either of the soluble lymphokines interleukin (IL )-4 or IL-13 which induce germline epsilon transcript expression, but alone is insufficient to trigger secretion of IgE. The second signal i s provided by a physical interaction between B cells and activated T c ells, basophils and mast cells, and it has been shown that the CD40/ C D40L pairing is crucial for mediating lgE synthesis. In HIGM1 syndrome , which is characterised by greatly decreased levels of IgG, IgA and I gE, there are mutations in CD40L resulting in a completely non-functio nal extracellular domain. CD40L is therefore playing a central role in Ig switching. Amongst the numerous pairs of surface adhesion molecule s, the CD23/CD21 pair seems to play a key role in the generation of Ig E. The CD23 molecule is positively and negatively regulated by factors which increase or decrease IgE production, re- spectively. Antibodies to CD23 have been shown to inhibit IL-4-induced human IgE production in vitro and to inhibit antigen-specific IgE responses in a rat model, in an isotype-selective manner. CD23 interacts with CD21 on B cells, preferentially driving IgE production. CD23 recognises two main epitop es on the CD21 molecule. One region consists of short consensus repeat sequences (SORs) 1-2 and the other of SCRs 5-8. In the latter region ASn370 and Asn295 are critical in the interaction with the lectin CD23 . Therefore, a restricted number of cytokines and surface molecules se ems to selectively regulate human IgE synthesis.