Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of membrane molecules primarily expressed in immune cells. Most of them are inhibitory receptors containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the… Click to show full abstract
Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of membrane molecules primarily expressed in immune cells. Most of them are inhibitory receptors containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic tail. On the cell surface, Siglecs are mostly bound by sialylated glycans on membrane molecules expressed in the same cell (cis-ligands). Although ligands of Siglecs are not efficiently identified by conventional methods such as immunoprecipitation, in situ labeling including proximity labeling is useful in identifying both cis-ligands and the sialylted ligands expressed by other cells (trans-ligands) of Siglecs. Interaction of the inhibitory Siglecs with cis-ligands including both those with and without signaling function modulates the inhibitory activity of Siglecs by multiple different ways. This interaction also modulates signaling function of the cis-ligands. So far, little is known about the role of the interaction between Siglecs and the cis-ligands. Nonetheless, recent studies showed that the inhibitory activity of CD22 (also known as Siglec-2) is regulated by endogenous ligands, most likely cis-ligands, differentially in resting B cells and those in which B cell antigen receptor (BCR) is ligated. This differential regulation plays a role in quality control of signaling-competent B cells and also partial restoration of BCR signaling in immunodeficient B cells.
               
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