Regulation of FcεRI Expression during Murine Basophil Maturation: The Interplay between IgE, Cell Division, and FcεRI Synthetic Rate

Abstract

Expression of FcεRI on basophils and mast cells is modulated by IgE Ab. Previous studies have noted in vivo receptor expression dynamics that are discordant with expectations derived from in vitro studies. The current study presents a formal hypothesis to explain the discordant observations and tests two assumptions that underlie a proposed model of receptor dynamics. After first showing that a murine model of receptor expression on basophils recapitulates observations made using human basophils, the effect of changes in IgE on basophil egress rates was examined. In the proposed model, egress rates from bone marrow (BM) were assumed to be unaffected by changes in IgE concentration. Egress was tested by examining the labeling of BM and peripheral blood (BL) basophils at various times after injection of BrdU with and without injection with IgE. The IgE Ab did not alter the appearance of BrdU label in peripheral BL basophils. In addition, BM and BL basophils were responsive to the elevations in IgE, with receptor expression increasing on BM basophils before BL basophils. It was also noted that BL basophils expressed ∼50% of the receptor density of BM basophils. There was a 3-fold greater synthetic rate of FcεRI on BM basophils that readily explained the difference. These results provide support for the proposed hypothesis of rapid changes in receptor expression being controlled by cell replacement. The studies also support a model whereby receptor expression is limited by cell division and that basophils, once mature, slow their rate of receptor synthesis.

Expression Profiling of Human Basophils: Modulation by Cytokines and Secretagogues

“…There is increasing evidence that changes observed in vitro may be blunted relative to changes that can occur in vivo . For example, synthesis of FcεRIα is markedly blunted in vitro , perhaps by 20 fold [ 46 , 47 ]. Likewise, synthesis of FcRβ is nearly non-existent in vitro [ 48 ], even with IL-3 present, but is clearly present in vivo .…”

Murine B Cells Regulate Serum IgE Levels in a CD23-Dependent Manner

“…One possible explanation is that only a limited number of unoccupied receptors exist on the surface of basophils and mast cells. Although quantifying the numbers of unoccupied receptors is difficult (39), it was clear that both basophils and mast cells had sufficient unoccupied receptors to bind exogenous IgE (Figure 2). Indeed, the regulation of surface FcεRI is thought to occur mainly through stabilization of unoccupied receptors after IgE binding with a dynamic balance between de novo IgE production and endocytosis of unoccupied receptors (40).…”

CD41 is a reliable identification and activation marker for murine basophils in the steady state and during helminth and malarial infections

“…This is evidenced by our results showing that during Nb infection, basophils cannot be identified via anti-FcεRI (Fig. 3A, [14,17]) because the FcεRI receptor accessibility is blocked by high IgE concentration in the serum [36]. Our analysis of sorted CD41 int CD45 int cells showed that they display almost exclusively basophil morphology from our cytospin experiments.…”

“…This is evidenced by our results showing that during Nb infection, basophils cannot be identified via anti‐FcεRI (Fig. A, ) because the FcεRI receptor accessibility is blocked by high IgE concentration in the serum .…”