This research will build on important recent findings by the investigator that human blood B lymphocytes can be induced to synthesize substantial quantities of IgE by the addition of very small quantities of purified recombinant human interleukin 4 (rHIL-4) in the presence of T cells. This has made possible for the first time the development of a reproducibly positive system for studying human IgE immunoregulation.
The aim are to evaluate 1) whether the addition of one or more other cytokines (or antibodies to such cytokines) to unfractionated blood mononuclear cells (MNC) can further increase (or decrease) the amount of IgE synthesis induced by an optimal or a suboptimal concentration of rhIL-4, 2) whether purified B cells stimulated with rhIL-4 and one or more additional cytokines will synthesize IgE in the absence of T cells, 3) whether direct T and B cell interaction must occur in such cultures for IgE synthesis to be stimulated and, if so, whether both cognate and non- cognate interaction will provide the necessary signal, 4) whether humans who synthesize excessive quantities of IgE in vivo produce more IL-4 than normal subjects. 5) whether the relative production of other cytokines (such as interferon 6, IL-5 or IL-6) hat counter or enhance the action of IL-4 is different by atopic and non-atopic blood MNC, 6) whether B cells from persons with excessive IgE production are more sensitive than B cells from normal donors to stimulation with rhIL-4 and 7) the mechanism of pokeweed mitogen's (PWM) inhibition of rhil-4-induced IgE synthesis and of the mutual inhibition of PWM and rhIL-4 on each's ability to induce IgG synthesis. This system for inducing human IgE synthesis in vitro makes possible a careful dissection of the roles of various cells and cytokines in the regulation of human IgE synthesis. Such information will be of great value in delineating at a cellular and molecular level the causative differences between humans who produce excessive quantities of IgE and those who do not. Once such differences are identified, this information could lead to major therapeutic advances for IgE-mediated allergic diseases.
