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,||,¶ Department of Microbiology, Department of Pediatrics, and || Department of Medicine, University of Alabama at Birmingham, and the ¶ Howard Hughes Medical Institute, Birmingham, Alabama 35294; and the ** Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021
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 the human natural killer (NK) and Fc receptors. Monoclonal and polyclonal antibodies produced against a recombinant PIR protein identified cell surface glycoproteins of
85 and 120 kD on B cells, granulocytes, and macrophages. A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common 
(FcRc) chain. Whereas PIR-B fibroblast transfectants expressed cell surface molecules of 120 kD, PIR-A transfectants expressed the 85-kD molecules exclusively intracellularly; PIR-A and FcRc cotransfectants expressed the PIR-A/ FcRc complex on their cell surface. Correspondingly, PIR-B was normally expressed on the cell surface of splenocytes from FcRc–/– mice whereas PIR-A was not. Cell surface levels 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 expression of PIR-B, an inhibitory receptor, and PIR-A, an activating receptor; demonstrate the requirement of FcRc chain association for cell surface PIR-A expression; and suggest that the level of FcRc chain expression could differentially affect the PIR-A/PIR-B equilibrium in different cell lineages.
Key Words: Fc receptor chain • activating receptor • inhibitory receptor • dendritic cells • innate immunity
H. Kubagawa and C.-C. Chen contributed equally to this work.
Abbreviations used: CY, cychrome; EC, extracellular domain; Fc
R, Fc receptor for IgA; FcR, Fc receptor for IgG; FcRc, Fc receptor common chain; ILT, Ig-like transcript; ITAM, immunoreceptor tyrosine–based activation motif; ITIM, immunoreceptor tyrosine–based inhibitory motif; KIR, killer inhibitory receptor; LIR, leukocyte Ig-like receptor; MIR, monocyte/macrophage Ig-like receptor; PIR, paired Ig-like receptor; SPIT, solid-phase immunoisolation technique.
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