Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B

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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