title: Binding the low affinity Fc epsilon R on B cells suppresses ongoing human IgE synthesis.
abstract: Our results support the hypothesis that binding the low affinity Fc epsilon R (Fc epsilon R-II, CD23) on IgE-secreting B cells, directly suppresses IgE production. IgE production from AF-10/U266 (a human IgE plasmacytoma) decreased upon incubation with anti-IgE mAb or IgE:anti-IgE immune complexes (IgE-IC). Synthesis was suppressed a maximum of 51% with 10 micrograms/ml of IgE-IC after a 24-h incubation. Spontaneous in vitro IgE synthesis from the B cells of highly atopic individuals was also inhibited in a similar fashion. This effect was isotype specific as IgA or IgG immune complexes did not alter IgE production from AF-10 nor did IgE-IC affect IgA or IgG synthesis from lymphoblastoid cell lines making IgG (GM1500 and RPMI 8866) or IgA (GM1056). U266/AF-10 cells displayed both membrane IgE (greater than 90%) and Fc epsilon R-II (23%). To evaluate the role of these membrane proteins in the observed suppression of IgE synthesis, we treated U266/AF-10 cells with IgE-IC that bound Fc epsilon R-II but could not bind membrane IgE, as the mAb used was directed against an idiotypic determinant on the myeloma IgE (PS) used to make the IgE-IC. Suppression was maximal (greater than 50%) with these complexes at 0.1 micrograms/ml and at a 1/1 ratio of mAb anti-IgE to human myeloma IgE. When IgE-IC were used that were constructed with heat denatured IgE or F(ab')2 fragments of IgE, suppression was abrogated indicating IgE-Fc epsilon R binding was required. Neither PS IgE nor mAb 5.1 (the components of IgE-IC) alone affected IgE synthesis. Furthermore, a mAb binding directly to CD23 suppressed IgE synthesis from AF-10 up to 60%. Using limiting dilution analysis, we determined that IgE production per AF-10 cell was constant (0.9 pg/cell/24 h), independent of cell density and cells incubated with IgE-IC were uniformly suppressed. To clarify the mechanism of IgE-IC-induced suppression on AF-10 cells, we assessed both the proliferative rate and cell cycle distribution upon incubation with IgE-IC. There was no correlation between IgE production and [3H]TdR incorporation by AF-10 cells incubated with IgE-IC or anti-CD23 mAb. The distribution of cells within the cell cycle was unaffected by these treatments, with 60% of the cells in G1. These results define a direct role for the Fc epsilon R-II on B cells in the regulation of ongoing IgE synthesis.
authors.affiliation: Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024.
authors.forename: E
authors.initials: E
authors.lastname: Sherr
authors.forename: E
authors.initials: E
authors.lastname: Macy
authors.forename: H
authors.initials: H
authors.lastname: Kimata
authors.forename: M
authors.initials: M
authors.lastname: Gilly
authors.forename: A
authors.initials: A
authors.lastname: Saxon
mesh_terms: D000911:Antibodies, Monoclonal / Q000502:physiology; D000936:Antigen-Antibody Complex / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D001666:Binding Sites, Antibody; D002453:Cell Cycle; D002460:Cell Line; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000502:physiology*; D008213:Lymphocyte Activation; D011961:Receptors, Fc / Q000378:metabolism* / Q000502:physiology; D017455:Receptors, IgE
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000944:Antigens, Differentiation, B-Lymphocyte; D007166:Immunosuppressive Agents; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E