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

The potential of the paired Ig-like receptors of activating (PIR-A) and inh ibitory (PIR-B) types for modifying an IgE antibody-mediated allergic respo nse was evaluated in mouse bone marrow-derived mast cells. Although mast ce lls produced both PIR-A and PIR-B, PIR-B was found to be preferentially exp ressed on the cell surface, where it was constitutively tyrosine phosphoryl ated and associated with intracellular SHP-1 protein tyrosine phosphatase. PIR-B coligation with the IgE receptor (Fc epsilon RI) inhibited IgE-mediat ed mast cell activation and release of serotonin. Surprisingly, the inhibit ory 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 Fc epsilon RI-bearing rat basophilic leukemia (RBL) cells transfected with con structs having mutations in the PIR-B cytoplasmic region. These results def ine 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.