Mast cells and company

Abstract

Classically, allergy depends on IgE antibodies and on high-affinity IgE receptors expressed by mast cells and basophils. This long accepted IgE/FcεRI/mast cell paradigm, on which the definition of immediate hypersensitivity was based in the Gell and Coomb's classification, appears too reductionist. Recently accumulated evidence indeed requires that not only IgE but also IgG antibodies, that not only FcεRI but also FcγR of the different types, that not only mast cells and basophils but also neutrophils, monocytes, macrophages, eosinophils, and other myeloid cells be considered as important players in allergy. This view markedly changes our understanding of allergic diseases and, possibly, their treatment.

Keywords: Fc receptors; allergy; anaphylaxis; antibodies; basophils; mast cells; neutrophils.

Figure 1

The interplay between myeloid and lymphoid cells in adaptive immune responses. Adaptive immune responses are initiated by the presentation of antigen by dendritic cells (DC). Cognate interactions with antigen-presenting cells activate naive T cells that proliferate and differentiate. T_H cells collaborate with specific B cells that proliferate and differentiate into Plasma Cells (P) that secrete antibodies (Induction phase). Antibodies diffuse throughout the body. When interacting with Fc Receptor-expressing myeloid cells and with specific antigen, antibodies induce a wide array of biological responses that depend on the cell type (Effector phase).

Figure 2

Murine and human receptors for the Fc portion (FcR) of IgE and IgG. This figure schematizes FcR for IgE and for IgG expressed by mouse and human myeloid cells.

Figure 3

Affinity of mouse and human FcR for homologous IgE and IgG subclasses. Affinity constants were determined by Plasmon resonance analysis. (Dierks et al., ; Hibbert et al., ; Nimmerjahn and Ravetch, ; Mancardi et al., ; Bruhns et al., 2009).

Figure 4

Tissue distribution of mouse and human FcR for IgE and IgG. The figure shows the relative expression of activating (red) and inhibitory (blue) IgE and IgG receptors of the immunoglobulin superfamily by murine and human hematopoietic cells. Gray bars show the expression of FcγRIIIB.

Figure 5

Anaphylactic properties of FcγRIIA^Tg in FcR-KO mice. The figure shows the expression of FcR in FcgRIIA^Tg mice used in our studies (left) and the magnitude of their responses in four models of anaphylaxis (right).