THE PAIRED IG-LIKE RECEPTOR PIR-B IS AN INHIBITORY RECEPTOR THAT RECRUITS THE PROTEIN-TYROSINE-PHOSPHATASE SHP-1

An emerging family of cell surface inhibitory receptors is characteriz ed by the presence of intracytoplasmic immunoreceptor tyrosine-based i nhibition motifs (ITIM). These ITIM-bearing inhibitory receptors, whic h are typically paired with activating isoforms, associate with Src ho mology domain 2-containing phosphatases following ITIM tyrosine phosph orylation. Two categories of phosphatases are recruited by the ITIM-be aring receptors: the protein-tyrosine phosphatases, SHP-1 and SHP-2, a nd the polyphosphate inositol 5-phosphatase, SHIP. The dynamic equilib rium of B cell activation is partially controlled by two well known IT IM-bearing receptors, CD22 and Fc gamma RIIB, a low affinity receptor for IgG. We describe here that a murine ITIM-bearing molecule, PIR-B, can also negatively regulate B cell activation. Tyrosine-phosphorylate d ITIMs allow PIR-B to associate with SHP-1 but not with SHIP. Engagem ent of PIR-B thereby initiates a SHP-1-dependent inhibitory pathway th at may play an important role in regulating B lymphocyte activation.