Influence of Genetic and Environmental Factors on Surface Expression and Occupancy of IgE Receptors and on Histamine Releasability of Mast Cells

Abstract

The relationship between the IgE load on mast cells and their secretory capacity when challenged with anti-IgE was studied in peritoneal cells obtained from rats of three different strains, Hooded Lister (HL), Wistar Kyoto (WKY) and Sprague-Dawley (SD). IgE was determined cytofluorometrically after labelling with FITC-conjugated anti-IgE before and after the saturation of the IgE receptors to provide a measure of the surface expression of IgE receptors (number of receptors available for bindings) as well as the IgE occupancy of the receptors (native IgE content). The secretory capacity of the mast cells was examined in vitro in terms of histamine release as a function of anti-IgE concentration. Mast cells obtained from HL and WKY rats were found to carry significantly higher levels of IgE receptors and IgE than the mast cells of SD rats bred and raised under the same conventional laboratory conditions. The mast cells of SD rats kept under barrier-maintained conditions carried significantly less IgE than the mast cells obtained from SD rats kept under conventional conditions, but their IgE receptor levels were similar. The IgE-mediated histamine-releasing capacity of the mast cells, evaluated in terms of maximum release or of the slopes of regression lines (histamine release versus anti-IgE concentration), was positively correlated to the levels of native IgE and IgE receptors in the three strains of rat combined. The mast cells obtained from WKY rats showed the highest secretory capacity in the three strains of rat examined, significantly higher than the mast cells of HL rats, even though the latter displayed similar levels of IgE and IgE receptors. These findings indicate that under basal conditions in these strains of rat the number of IgE receptors available for binding as well as the IgE occupancy is determined by both the genetic background and the environment. The IgE-mediated histamine release appeared to be largely, but not exclusively a function of the number of IgE-receptor complexes on the mast-cell surface. The difference in histamine-releasing capacity between WKY and HL rats suggests that genetic factors may control the secretory capacity of the mast cells also through mechanisms other than those involving the expression of IgE receptors and the binding of IgE by the mast cells.

IgE Generation and Mast Cell Effector Function in Mice Deficient in IL-4 and IL-13

“…The relatively strong induction of anti-IgEmediated PCA responses in association with only marginal increases in serum IgE following immunization is consistent with observations that even low level IgE receptor occupancy can support the degranulation of basophils (62,63) or mast cells (43). The increased IgE levels and effector responses following immunization confirm and extend previous reports of OVA-induced anaphylactic responses in IL-4R␣ Ϫ/Ϫ mice (19), by indicating that neither IL-4 nor IL-13 is absolutely required for IgE production or for IgE-dependent mast cell activation in vivo.…”

“…As histamine releasability has been shown to correlate with the number of IgE molecules on mast cells (43), this response was compared with or without exposure of the cells to exogenous IgE in vitro. Maximum release was quantitated following solubilization of the cell membranes with Triton X-100.…”

Immune Responses to a <i>Nippostrongylus</i> <i>brasiliensi</i><i>s</i> Infection in Athymic and Euthymic Rats: Surface Expression of IgE Receptors, IgE Occupancy and Secretory Ability of Mast Cells

“…31, 58] including the present one, 70-80% of the IgE receptors on mast cells available for binding were found to be occupied by IgE. The IgE appears to derive from a T-cell-independent IgE synthesis influenced by genetic and environmental factors [59], The question is why such a large majority of the IgE receptors need to be occupied un der normal conditions and how this biological phenomenon relates to the function of the mast cell in vivo. We propose the hypothesis that the IgE molecules on the mast cell may play a regulatory role to prevent serious harmful effects of a massive degranulation when mast cells are exposed to spe cific allergen.…”

Clinical consequences of mast cell heterogeneity

“…These data indicate that the heterogeneous responses of mast cells are influenced by factors more complex than differential receptor expression. This concept is supported by findings that the response of mast cells to immunological stimuli is not necessarily determined by the surface density of IgE receptors [27,28].…”