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 characterized by the presence of intracytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIM). These ITIM-bearing inhibitory receptors, which are typically paired with activating isoforms, associate with Src homology domain 2-containing phosphatases following ITIM tyrosine phosphorylation. Two categories of phosphatases are recruited by the ITIM-bearing receptors: the protein-tyrosine phosphatases, SHP-1 and SHP-2, and the polyphosphate inositol 5-phosphatase, SHIP. The dynamic equilibrium of B cell activation is partially controlled by two well known ITIM-bearing receptors, CD22 and FcγRIIB, 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-phosphorylated ITIMs allow PIR-B to associate with SHP-1 but not with SHIP. Engagement of PIR-B thereby initiates a SHP-1-dependent inhibitory pathway that may play an important role in regulating B lymphocyte activation.

一类新兴的细胞表面抑制性受体家族，以胞浆内免疫受体酪氨酸抑制基序（intracytoplasmic immunoreceptor tyrosine-based inhibition motifs, ITIM）为标志性特征。这类携带ITIM的抑制性受体通常与激活性同工型配对，在ITIM的酪氨酸残基发生磷酸化后，可与含Src同源结构域2的磷酸酶相结合。ITIM携带型受体可招募两类磷酸酶：蛋白酪氨酸磷酸酶SHP-1、SHP-2，以及多磷酸肌醇5-磷酸酶SHIP。B细胞活化的动态平衡，部分受到两种经典ITIM携带型受体的调控——CD22与IgG低亲和力受体FcγRIIB。本研究报道，一种小鼠来源的ITIM携带型分子PIR-B同样可负向调控B细胞活化。经酪氨酸磷酸化的ITIM可使PIR-B与SHP-1结合，但无法与SHIP结合。因此，PIR-B的交联会启动一条依赖SHP-1的抑制通路，该通路可能在调控B淋巴细胞活化的过程中发挥重要作用。