Low‐affinity receptors (Fc epsilon R) and secreted factors (IgE‐BF) which bind to immunoglobulins of the IgE isotype play a key role in the regulation of human IgE synthesis. We report here the cloning of a cDNA coding for the Fc epsilon R of the human B‐lymphoblast cell line RPMI 8866. The nucleotide sequence of this cDNA predicts a polypeptide with 321 amino acids and a mol. wt of 36,281 daltons. A functional Fc epsilon R capable of binding IgE was expressed in Chinese hamster ovary cells after stable transformation with the cDNA which had been cloned into a mammalian expression vector. Amino acid sequence analysis of IgE‐BF purified from RPMI 8866 cells revealed an amino‐terminal sequence of 19 residues which coincides with the predicted amino acid sequence of the Fc epsilon R, starting at residues 148 and 150. A computer search with the translated amino acid sequence of the Fc epsilon R revealed a domain of 120 amino acids having striking homology to the human asialoglycoprotein receptors.

Several pitfalls may affect studies on human IgE synthesis in vitro. In this paper, the requirement for stringent specificity of the anti-IgE antibodies used and for assessment not only of IgE detectable in culture supernatants but also as cell-associated IgE is emphasized. The use of cycloheximide-treated cultures as controls also leaves wishes open. Activated, human T cells and T cell hybridomas produce IgE-binding factors, which may be detected by a sensitive in vitro test and which may apparently also become the endeavour of synthesis by molecular biological techniques. Although the evidence available in rodents for the role of IgE-binding factors in modulating IgE synthesis has not yet been fully reproduced by us in man, the fact that classical IgE-enhancing procedures in rodents (e.g. radiotherapy, T cell suppression) also affect IgE production in man leads to believe that similar immunoregulation mechanisms apply to the various mammalian species studied so far.