Biochemical nature and cellular distribution of the paired immunoglobulin-like receptors, PIR-A and PIR-B

PIR-A and PIR-B, paired immunoglobulin-like receptors encoded, respectively , by multiple Pira genes and a single Pirb gene in mice, are relatives of t he human natural killer (NK) and Fc receptors. Monoclonal and polyclonal an tibodies produced against a recombinant PIR protein identified cell surface glycoproteins of similar to 85 and similar to 120 kD on B cells, granulocy tes, and macrophages. A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common gamma (FcR gamma c) chain. Whereas PIR-B fibroblast transfectants expressed cell surfa ce molecules of similar to 120 kD, PIR-A transfectants expressed the simila r to 85-kD molecules exclusively intracellularly; PIR-A and FcR gamma c cot ransfectants expressed the PIR-A/ FcR gamma c complex on their cell surface . Correspondingly, PIR-B was normally expressed on the cell surface of sple nocytes from FcR gamma c(-/-) mice whereas PIR-A was not. Cell surface leve ls of PIR molecules on myeloid and B lineage cells increased with cellular differentiation and activation. Dendritic cells, monocytes/macrophages, and mast cells expressed the PIR molecules in varying levels, but T cells and NK cells did not. These experiments define the coordinate cellular expressi on of PIR-B, an inhibitory receptor, and PIR-A, an activating receptor; dem onstrate the requirement of FcR gamma c chain association for cell surface PIR-A expression; and suggest that the level of FcR gamma c chain expressio n could differentially affect the PIR-A/PIR-B equilibrium in different cell lineages.