Regulation of IgD-Receptor Expression on Murine T Cells: I. Characterization and Metabolic Requirements of the Process Leading to Their Expression

Receptors for IgD (IgD-R) are found on murine CD4+ T cells and T cell clones. Previous work has shown that incubation with aggregated (but not monomeric) IgD causes the rapid upregulation of IgD-R and enables the T cells to respond with augmented helper function in antibody production. In the present study, IgD-R upregulation is shown to be (a) rapid, reaching plateau levels by 60 min, (b) independent of de novo protein or RNA synthesis, and (c) only slightly reduced at 4°C. The IgD-R+ T cells present both before and after upregulation of IgD-R expression are predominantly resting T cells, whose ability to rosette with IgD-SRBC is inhibited by soluble IgD. The upregulation of IgD-R, even after overnight exposure to IgD, does not cause any detectable change in the expression of other T cell surface markers. Also characteristic of resting T cells is that they exhibit IgD-R in response to IL-2 and IL-4 only after overnight incubation with these cytokines, and fail to respond at all to IL-1. In contrast, cloned Th2 cells, expressing IL-1 and IL-2 receptors, show IgD-R upregulation after a 2-hr exposure to IL-1 or IL-2. GM-CSF, TNF-α IL-6, and IL-10 do not modulate IgD-R expression. T hybridoma cells constitutively express much higher IgD-R levels than resting splenic T cells and can be stained with aggregated IgD followed by FITC-anti-IgD. Their levels of IgD-R expression decrease, as assayed both by rosetting and by staining, on 4-14 hr of incubation with tunicamycin or deoxynojirimycin, suggesting that N-linked glycosylation and oligosaccharide processing, respectively, are needed for continued expression of IgD-R. Tunicamycin-treated cells without detectable IgD-R on their surface still show IgD-binding protein in the cell extracts, suggesting that surface expression is more dependent on glycosylation of the IgD-R molecules than on the ability to bind IgD. Ca2+ ions are needed for optimal binding of IgD to IgD-R, in line with previous findings showing IgD-R to be lectin-like in binding carbohydrate rather than peptide regions of the IgD molecule.