Regulation of Fc epsilon R2/CD23 gene expression by cytokines and specific ligands (IgE and anti-Fc epsilon R2 monoclonal antibody). Variable regulation depending on the cell types

Abstract

The regulation of human low affinity FcR for IgE (Fc epsilon R2/CD23) and the soluble Fc epsilon R2 [IgE binding factor (BF)] of monocyte (U937), T (ED), and B (JIJOYE) cell lines was examined by anti-Fc epsilon R2 mAb (H107, Mab176) and the cDNA probe for Fc epsilon R2. The effect of IL-4 and IFN-gamma on Fc epsilon R2 regulation was variable among these three cell lines. IL-4 and IFN-gamma enhanced the Fc epsilon R2 gene expression and the production of Fc epsilon R2 and IgE-BF on U937, whereas IL-4 and IFN-gamma had no significant effect on the Fc epsilon R2 expression on ED. On JIJOYE, IL-4 enhanced the Fc epsilon R2 and IgE-BF production on both protein and mRNA levels. In U937 and JIJOYE cells, there was a marked increase of Fc epsilon R2 mRNA after combined stimulation with IFN-gamma and IL-4. However, in JIJOYE cells, there was a dissociation between the surface expression of Fc epsilon R2 and Fc epsilon R2 mRNA treated with IFN-gamma plus IL-4. In these cells. IFN-gamma even down-regulated the IL-4-induced expression of surface Fc epsilon R2. Stimulation of JIJOYE cells with both IFN-gamma and IL-4 resulted in the increase of the IgE-BF in the supernatant, suggesting that IFN-gamma enhanced the release of IgE-BF from Fc epsilon R2. The results indicated that Fc epsilon R2 and IgE-BF expression is regulated by IFN-gamma at least on two different levels: on transcriptional levels and the levels of cleavage of the surface Fc epsilon R2 to release soluble Fc epsilon R2 (IgE-BF). Ligands binding to the Fc epsilon R2 such as IgE and anti-Fc epsilon R2 mAb enhanced the surface expression of Fc epsilon R2 on these Fc epsilon R2(+) cell lines. This was mainly due to the surface accumulation of the receptors on JIJOYE and U937. However, the stimulation of ED by H107 and anti-Fc epsilon R2 mAb significantly enhanced the mRNA expression, indicating that Fc epsilon R2 synthesis may also be up-regulated by the specific ligands in some cell types.