Importance in understanding the events resulting in IgE production and therefore allergic disease is an understanding of B cell triggering events in the IgE response. One potential target to control IgE production has long been the lymphocyte low affinity receptor for IgE (FcepsilonRII) also known as CD23. The recent finding that CD23 interacts specifically with CD21 (complement receptor type 2 and receptor for Epstein Barr virus) brings together two formerly disparate areas of B cell biology. The overall objective of this application is to explore the effects of the CD23/CD21 interaction, especially with respect to IgE production. We have recently found that CD23 interacts with itself to form an oligomeric structure and that this oligomeric study is critical to interaction with its classic ligand, IgE. The importance of oligomerization in interaction with CD21 will be determined. Both CD21 and CD23 have been shown to influence B cell activation parameters. We will determine if the CD21/CD23 interaction will itself either directly or indirectly influence B cell activation. We hypothesize that a significant enhancement of B cell activation will be seen as a result of this interaction, especially when B cells are subjected to a limiting amount of activating agents. Both the specificity and outcome of any effect, especially with regard to IgE production will be ascertained by using mabs, IgE or soluble CD23 to block the interaction. A number of murine model systems will be incorporated into the study, including IgE production via LPS and IL-4, CD-40 ligand and IL-4 and in vitro germinal center cultures. Finally, we will determine the effect that spontaneous enhanced CD23 levels have on B cell activation/differentiation in general and CD23/CD21 interaction in particular. This will be done via production of transgenic mice with CD23 under the control of the kappa chain enhancer/promoter which will result in high level CD23 expression on all mature B cells. The phenotype of these mice will be determined; of special interest is whether the B cells of these mice are hyperreactive to stimulation and whether germinal center development and IgE production in both in vitro and in vivo models is effected.
