Regulation of Immunoglobulin E Biosynthesis

A crucial role of Immunoglobulin E (IgE) antibodies in reaginic (Type I) hypersensitivity immediately raised a question as to whether the antibody response can be suppressed. To achieve this goal, however, it is possible to lear cellular mechanisms involved in the IgE antibody response. The purpose of this chapter is to summarize some unique features for the antibody response of the IgE isotype and to discuss possible approaches to controlling the same. The IgE antibody response in inbred mouse strains provided most useful information on the mechanisms of IgE synthesis. However, in vitro IgE antibody responses by murine lymphoid cells have been most difficult to reproduce. When mice of a good IgE producer strain were immunized with alum-absorbed antigen for the persistent IgE antibody response, their spleen cells spontaneously released a substantial amount of IgE antibodies. Dissociation between the IgE and IgG antibody responses raised the possibility that the IgE antibody response may be regulated not only by antigen-specific helper and suppressor T cells but also by a mechanism selective for this isotype. Because the infection of antigen-primed rats with Nb selectively potentiated the IgE antibody response and the IgE-specific potentiation is dependent on T cells, it was anticipated that T cells of Nb-infected rats would selectively enhance the differentiation of IgE B cells to IgE-forming cells. Either regulation of the IgE antibody response by means of antigen-specific mechanisms has been attempted through tolerization of B cells or manipulation of the population of T cells that regulate the differentiation of B cells to IgE-forming cells. Another approach to regulating the antihapten IgE antibody response is to induce antiidiotypic antibodies. If the antihapten antibodies are restricted to certain idiotypes, idiotype-specific regulation may be applied. The third approach is to regulate the IgE antibody response by inducing antigen-specific suppressor T cells. It has been shown that intravenous injections of a soluble antigen without adjuvant into naive mice facilitate the generation of antigen-specific suppressor T cells.