Establishment of antigen-specific IgE transgenic mice to study pathological and immunobiological roles of IgE in vivo.

We have established transgenic mice that carry the genes coding for heavy and light chains of TNP-specific IgE. They produced high titers of TNP-specific IgE (20-40 microg/ml in serum) and their mast cells were heavily loaded with IgE. The level of FcepsilonRI expression on their mast cells was 6-8 times higher than that in non-transgenic littermates. The expression of low-affinity IgE receptor FcepsilonRII (CD23) on splenic B cells was also 6-8 times higher in the transgenic mice. Consistent with this, substantial amounts of IgE were detected on B cells in the transgenic mice. When challenged with i.v. administration of the corresponding antigen, the transgenic mice exhibited systemic anaphylactic symptoms such as a drastic drop of body temperature and extravasation of administered dye. Biphasic (immediate and delayed) ear swelling response was also elicited in a TNP-specific manner by epicutaneous antigen challenge without any prior sensitization. Thus, IgE produced in the transgenic mice was found to be biologically active to induce both local and systemic allergic reactions in vivo upon the challenge of the corresponding antigen. Taken together, the antigen-specific IgE transgenic mice established for the first time in this study appear to provide an attractive model system to study the pathological roles of IgE in acute and chronic phases of allergic inflammation as well as their immunobiological roles in vivo. They may also be useful to develop novel therapeutic strategies for atopic disorders.