The murine lymphocyte receptor for IgE, with regard to both structure and function is the focus of this application. Intact FceR levels increase during B cell activation in the presence of interleukin 4 (IL-4) suggesting a role for the FceR in B cell activation. Anti-FceR both in the soluble and sepharose bound form will be tested for the capacity to either directly activate B lymphocytes or to influence B cell activation by anti- Immunoqlobulin. Parameters to be measured include calcium influx, cell size changes, phosphatidyl inositol levels and Ig production. The FceR spontaneously releases lower molecular fragments via proteolysis at the cell surface and preliminary evidence suggests that these fragments enhance the level of IgE synthesis in the presence of IL-4. This phenomena will be further studied with regard to isotype specificity, role of FceR carbohydrate in the biologic activity and molecular size of the FceR fragment involved. In addition, it will be determined if the fragment interacts with a specific component on the B cell membrane. The site of interaction of IgE with the FceR is important with regard to receptor degradation and the location of this site will be explored in detail, both by using anti-peptide antibodies, mimicking specific areas of the FceR and by using crosslinking reagents that will label the site(s) of close proximity with IgE. Antibodies against the site of the FceR that interacts with IgE will also be tested for their capacity to induce FceR upregulation, analogous to IgE and their effect on IgE synthesis will be determined. The low affinity FceR on macrophages and T cells will be further investigated with regard to physiochemical relationship to the B cell FceR, association with other membrane components and regulation at the cell surface. The overall aim is to gain further insight into the structure and regulation of the low affinity FceR and to determine if FceR/anti-FceR related components are useful in the regulation of IgE synthesis.
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