Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B
Takahiro Uehara, Mathieu Bléry, Dong-Won Kang, Ching-Cheng Chen, Le Hong Ho, G. Larry Gartland, Fu-Tong Liu, Eric Vivier, Max D. Cooper, Hiromi Kubagawa
Takahiro Uehara, Mathieu Bléry, Dong-Won Kang, Ching-Cheng Chen, Le Hong Ho, G. Larry Gartland, Fu-Tong Liu, Eric Vivier, Max D. Cooper, Hiromi Kubagawa
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Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B

Abstract

The potential of the paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) types for modifying an IgE antibody–mediated allergic response was evaluated in mouse bone marrow–derived mast cells. Although mast cells produced both PIR-A and PIR-B, PIR-B was found to be preferentially expressed on the cell surface, where it was constitutively tyrosine phosphorylated and associated with intracellular SHP-1 protein tyrosine phosphatase. PIR-B coligation with the IgE receptor (FcεRI) inhibited IgE-mediated mast cell activation and release of serotonin. Surprisingly, the inhibitory activity of PIR-B was unimpaired in SHP-1–deficient mast cells. A third functional tyrosine-based inhibitory motif, one that fails to bind the SHP-1, SHP-2, and SHIP phosphatases, was identified in parallel studies of FcεRI-bearing rat basophilic leukemia (RBL) cells transfected with constructs having mutations in the PIR-B cytoplasmic region. These results define the preferential expression of the PIR-B molecules on mast cells and an inhibitory potential that can be mediated via a SHP-1–independent pathway.

Authors

Takahiro Uehara, Mathieu Bléry, Dong-Won Kang, Ching-Cheng Chen, Le Hong Ho, G. Larry Gartland, Fu-Tong Liu, Eric Vivier, Max D. Cooper, Hiromi Kubagawa

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Comparison of surface expression of FcγRIIB/PIR chimeric receptors among...
Comparison of surface expression of FcγRIIB/PIR chimeric receptors among various stable transfectants. RBL-2H3 rat basophilic leukemia cells were transfected by electroporation with various types (YYYY, FYFF, YY, YF, and Δ712) of chimeric construct (FcγRIIB/PIR-B). These constructs encode the extracellular (EC), transmembrane (TM), and the first six amino acids of the cytoplasmic tail of the mouse FcγRIIB1 (open portions of bars) and fused with different intracytoplasmic regions (IC) of the mouse PIR-B (filled portions of bars) as depicted in the right panel. Four cytoplasmic tyrosine (Y) residues are also indicated. For the left panel, stably transfected cells were sequentially incubated with 2.4G2 rat mAb and FITC-labeled goat anti-rat Ig antibody (filled profile) or with BC4 mouse IgE mAb and FITC-labeled goat anti-mouse Ig antibody (thick line) in order to determine their cell surface levels of FcγRIIB/PIR-B chimeric receptors and endogenous FcεRI by flow cytometry. Irrelevant mouse IgG (thin line) was used as a control to obtain a background staining.