Molecular mechanism of paired immunoglobulin­ like receptor B (PIR-B)-mediated inhibitory signal

B cell express paired immunoglobulin-like receptor B (PIR-B) contains four potential ITIMs (immunoreceptor tyrosine-based inhibitory motifs) in the cytoplasmic domain. Coligation of PIR-B with B cell antigen receptor (BCR) blocks antigen-induced B cell activation. This inhibition is mediated in part by recruitment of SH2-containing tyrosine phosphatases SHP-1 and SHP-2 to the phosphorylated ITIMs in the cytoplasmic domain of PIR-B. PIR-B ligation inhibits the BCR-induced tyrosine phosphorylation of Igα/Igβ, Syk, Btk, and phospholipase C (PLQ-γ2. Overexpression of a catalytically inactive form of SHP-1 prevents the PIR-B-mediated inhibition of tyrosine phosphorylation of Syk, Btk, and PLC-γ2. Dephosphorylation of Syk and Btk mediated by SHP-1 leads to a decrease of their kinase activity, which in turn inhibits tyrosine phosphorylation of PLC-γ2. In addition, Lyn is required for tyrosine phosphorylation of PIR-B.