Mast cell regulation via paired immunoglobulin-like receptor PIR-B.

Activating (PIR-A) and inhibitory (PIR-B) isoforms of the paired immunoglobulin (Ig)-like receptor family have been evaluated for their modulating potential in mast cell responses to IgE antibody and mast/stem cell growth factor (SCF). Mast cells produce PIR-A and PIR-B, but PIR-B was found to be predominantly expressed on the cell surface, where it was constitutively tyrosine phosphorylated and associated with SHP-1 tyrosine phosphatase. Efficient coligation of PIR-B with FcepsilonRI inhibited IgE-induced mast cell activation and serotonin release. PIR-B and c-kit (or mast/SCF receptor) coligation also inhibited SCF-induced mast cell responses. The PIR-B inhibitory activity was unimpaired in SHP-1-deficient mast cells, perhaps because of non-SHP-1-binding tyrosine-based inhibitory motif in the cytoplasmic tail of PIR-B. This analysis suggests that PIR-B may serve to control mast cell activity.