Regulation of Human IgE Synthesis

The capacity to mount an IgE antibody response to antigen differentiates normal from allergic individuals. The frequent association of high serum IgE with T cell immunodeficiencies suggest a role for T cells in the regulation of human IgE. Peripheral blood lymphocytes (PBL) from allergic individuals spontaneously secrete IgE in vitro whereas normal PBL do not. Unlike the situation with other isotypes the polyclonal B-cell activators, pokeweed mitogen, and Epstein-Barr virus, do not induce IgE synthesis in normal B cells. However, normal B cells synthesize IgE when cultured with T cell clones that recognize determinants expressed by the B cells. B cells from allergic subjects but not from normal subjects are induced to secrete IgE via a bystander effect when cultured with T cell clones which are stimulated by antigenic determinants not expressed by the B cells. T cells with Fe receptors for IgE can be isolated from patients with hyper IgE syndrome and maintained as long term continuous T cell lines or T-T hybridomas. These cells secrete IgE binding factors which enhance IgE synthesis by preactivated IgE bearing B cells from allergic subjects but not resting B cells from normal donors. The phenotype of these Fe R+ IgE-potentiating T cell lines are predominantly T3+ T4+ Ia+. IgE binding factors have been isolated from normal serum and selectively suppress IgE synthesis. In contrast IgE binding factors isolated from patients with hyper IgE syndrome contain IgE-potentiating activity as well as IgE suppressor activity. These results suggest that in allergic individuals IgE B cells are activated by T cells and their antibody secretion is modulated by IgE binding factors