Identification, characterization and leucocyte expression of Siglec-10, a novel human sialic acid-binding receptor

Abstract

Here we characterize Siglec-10 as a new member of the Siglec family of sialic acid-binding Ig-like lectins. A full-length cDNA was isolated from a human spleen library and the corresponding gene identified. Siglec-10 is predicted to contain five extracellular Ig-like domains and a cytoplasmic tail containing three putative tyrosine-based signalling motifs. Siglec-10 exhibited a high degree of sequence similarity to CD33-related Siglecs and mapped to the same region, on chromosome 19q13.3. The expressed protein was able to mediate sialic acid-dependent binding to human erythrocytes and soluble sialoglycoconjugates. Using specific antibodies, Siglec-10 was detected on subsets of human leucocytes including eosinophils, monocytes and a minor population of natural killer-like cells. The molecular properties and expression pattern suggest that Siglec-10 may function as an inhibitory receptor within the innate immune system.

Sialoside Specificity of the Siglec Family Assessed Using Novel Multivalent Probes

“…The preference of sialoadhesin (mSiglec-1) and MAG (mSiglec-4) for the NeuAc␣(2-3)Gal sequence over the NeuAc␣(2-6)Gal sequence (26,27,30,32,34,36) is consistent with the 2-3-and 5-7-fold increased affinity, respectively, for sialosides with the ␣2-3 linkage (4 and 5) over those with the ␣2-6 linkage (12 and 13), in good agreement with results obtained by Strenge et al (26). A preference of Siglecs-9 and -10 for sialosides with the ␣2-3 linkages seen here (1.5-2-fold) was not recognized previously using multivalent probes (51,53,59,61). Yamaji et al (28) demonstrated a unique preference of Siglec-7 for the NeuAc␣(2-8)NeuAc sequence found in the ganglioside GD3 based on competitive inhibition of binding to a multivalent GD3-bovine serum albumin probe using ganglioside micelles.…”

“…Several reports (25,26,28,39,40) have evaluated the specificity of one or several siglecs using competitive inhibition of multivalent binding assays by monovalent sialosides analogous to the studies reported here. However, most have used multivalent assays based on binding of siglecs to sialosides attached to a polyacrylamide or other polymeric carrier (1,34,37,49,(52)(53)(54)(55)(57)(58)(59), to gangliosides adsorbed to microtiter plates (30,36,38) or to neo-glycoprotein conjugates (27,28).…”

SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders

“…16 These mice develop a B-cell hyperplasia of the CD5 + lineage in the peritoneal cavity that evolves into a frank B-cell leukemia/lymphoma with variable penetrance (from 10% annually in Eµ-BRD2 mice to 100% in Eµ-TCL1 mice) and at different ages (from 7 months in Eµ-BRD2 mice to 12-18 months in CLL mouse models). Such heterogeneous evolution indicates that the expansion and progression of malig- Federico Caligaris-Cappio, 1,7,8 and Paolo Ghia…”

“…We also analyzed T lineage cells over time, although T-SIGLEC-G deficiency promotes B-cell lymphoma haematologica | 2014; 99 (8)cell numbers were reportedly stable in 2-to 3-month old Siglecg −/− mice. 1 In accordance with this previous report, the percentage of splenic CD3 + T cells was unmodified at 5, 10 and 16 months of age.…”

“…[1][2][3][4][5][6][7] In human B lymphocytes a similar function is exerted by the ortholog, SIGLEC10, a member of the CD33-related family of SIGLECs. 8,9 Both SIGLEC-G and SIGLEC10 are also able to suppress Toll-like receptor-mediated activation of dendritic cells, thereby dampening the pro-inflammatory response induced by danger-associated molecular patterns. + polyclonal B-cell population in the spleen and especially in the peritoneal cavity.…”