Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B
Takahiro Uehara, … , Max D. Cooper, Hiromi Kubagawa
Takahiro Uehara, … , Max D. Cooper, Hiromi Kubagawa
Published October 1, 2001
Citation Information: J Clin Invest. 2001;108(7):1041-1050. https://doi.org/10.1172/JCI12195.
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Article

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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Figure 1

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Cell surface expression of PIR molecules on cultured mast cells. Nonadhe...
Cell surface expression of PIR molecules on cultured mast cells. Nonadherent cells from the bone marrow of (a) wild-type mice (C57BL/cJ) and (b) FcεRIα–/– mice and from the neonatal spleens of (c) wild-type mice (C3H/HeJ) and (d) me/me mice were cultured for 6 weeks with rIL-3. Cells were sequentially incubated with the PE-labeled 6C1 anti-PIR mAb, biotinylated ACK-2 anti–c-kit mAb, and APC-labeled streptavidin or with rat IgE anti-DNP mAb (dark histogram) and FITC-labeled goat anti-rat Ig antibodies before analysis by flow cytometry. Isotype-matched control rat mAb’s were used to set the quadrants for immunofluorescence analysis, and unstained background controls are indicated by open histograms.