Inhibitory and stimulatory functions of paired Ig-like receptor (PIR) family in RBL-2H3 cells

In this study, we demonstrate potent regulatory function of the murine killer cell inhibitory receptor-like molecules, paired Ig-like receptors (PIRs) or p91, using chimeric receptors expressed on the rat basophilic leukemia cell line RBL-2H3. One of the chimeras, which has the transmembrane and cytoplasmic domain of PIR-B fused to the extracellular portion of type IIB receptor for IgG, was able to inhibit the type I receptor for IgE- mediated degranulation response upon coaggregation. This chimera also suppressed cytoplasmic Ca²⁺ mobilization in the presence and absence of calcium ion in the extracellular medium. Tyrosine to phenylalanine point mutations at the third and fourth immunoreceptor tyrosine-based inhibitory motif-like sequences of PIR-B attenuated the inhibitory effects on degranulation and on cytoplasmic Ca²⁺ mobilization, indicating the important role of these tyrosines for the delivery of negative signal. In contrast, the cross-linking of another chimeric receptor composed of the type IIB receptor for IgG extracellular portion and the transmembrane and short cytoplasmic sequence of PIR-A elicited Ca²⁺ mobilization and degranulation. These results indicate that PIR molecules may regulate cellular functions both positively and negatively.