Human B-lymphocytes Express α2-6-Sialylated 6-Sulfo-N-acetyllactosamine Serving as a Preferred Ligand for CD22/Siglec-2

Kimura, Naoko; Ohmori, Katsuyuki; Miyazaki, Kohji; Izawa, Masako; Matsuzaki, Yuji; Yasuda, Yosuke; Takematsu, Hiromu; Kozutsumi, Yasunori; Moriyama, Akihiko; Kannagi, Reiji

doi:10.1074/jbc.m702341200

Cited by 74 publications

(65 citation statements)

References 43 publications

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“…Recent reports demonstrate that high affinity cis ligands of CD22 are downregulated on B-cells during differentiation in germinal centers (54,55), favoring binding of CD22 on activated B-cells to trans ligands on other contacting cells. trans ligands of CD22 have been documented to exist on B-cells, T-cells, monocytes, endothelial cells, and dendritic cells (9,10,13,18,56).…”

Section: Discussionmentioning

confidence: 99%

In Situ trans Ligands of CD22 Identified by Glycan-Protein Photocross-linking-enabled Proteomics

Ramya

Weerapana

Liao

et al. 2010

Molecular & Cellular Proteomics

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CD22, a regulator of B-cell signaling, is a siglec that recognizes the sequence NeuAc␣2-6Gal on glycoprotein glycans as ligands. CD22 interactions with glycoproteins on the same cell (in cis) and apposing cells (in trans) modulate its activity in B-cell receptor signaling. Although CD22 predominantly recognizes neighboring CD22 molecules as cis ligands on B-cells, little is known about the trans ligands on apposing cells. We conducted a proteomics scale study to identify candidate trans ligands of CD22 on B-cells by UV photocross-linking CD22-Fc chimera bound to B-cell glycoproteins engineered to carry sialic acids with a 9-aryl azide moiety. Using mass spectrometrybased quantitative proteomics to analyze the cross-linked products, 27 glycoproteins were identified as candidate trans ligands. Next, CD22 expressed on the surface of one cell was photocross-linked to glycoproteins on apposing B-cells followed by immunochemical analysis of the products with antibodies to the candidate ligands. Of the many candidate ligands, only the B-cell receptor IgM was found to be a major in situ trans ligand of CD22 that is selectively redistributed to the site of cell contact upon interaction with CD22 on the apposing cell. Molecular & Cellular Proteomics 9:1339 -1351, 2010. Glycan-binding proteins (GBPs)1 mediate diverse aspects of cell communication through their interactions with their counter-receptors comprising glycan ligands carried on cell surface glycoproteins and glycolipids. Identification of the in situ counter-receptors of glycan-binding proteins is problematic due to the fact that the vast majority of the glycoproteins of a cell will carry highly related glycan structures because they share the same secretory pathway that elaborates their glycans post-translationally en route to the cell surface. Thus, although many glycoproteins will carry the glycan structure recognized by a GBP, the challenge is to determine whether one, several, or all of these cell surface glycoproteins (and glycolipids) are recognized in situ as physiologically relevant counter-receptors (1-4). Standard in vitro methods, such as co-precipitation from cell lysates or Western blotting using binding protein probes, are useful for identifying glycoproteins that contain the glycan structure recognized by the GBP. However, these may not be relevant ligands in situ due to constraints imposed by their microdomain localization and the geometric arrangement of their glycans relative to the GBP presented on the apposing cell.In this report, we examine the in situ ligands of CD22 (Siglec-2), a member of the siglec family and a regulator of B-cell receptor (BCR) signaling that recognizes glycans containing the sequence NeuAc␣2-6Gal as ligands (2, 5, 6). Regulation of BCR signaling by CD22 is effected by its proximity to the BCR through recruitment of a tyrosine phosphatase, SHP-1, which is in turn influenced by CD22 binding to its glycan ligands (6). Glycoproteins bearing CD22 ligands are abundantly expressed on B-cells and bind to CD22 in cis (on the sa...

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Section: Discussionmentioning

confidence: 99%

In Situ trans Ligands of CD22 Identified by Glycan-Protein Photocross-linking-enabled Proteomics

Ramya

Weerapana

Liao

et al. 2010

Molecular & Cellular Proteomics

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“…Both GlcNAc6ST-1 and HEC-GlcNAc6ST are known to be involved in its synthesis (9). More recently, endothelial cells have been known to also express ␣2-6 sialylated 6-sulfo-LacNAc, which is suggested to serve as a preferred ligand for CD22/Siglec-2 (14). Several genes are known to be regulated by tandem NF-B and GATA motifs in endothelial cells, such as erythropoietin (33) and VCAM-1 (34,35).…”

Section: Discussionmentioning

confidence: 99%

“…As sulfation at the C-6Ј position of the galactose residue in lactosamine is postulated to require prior 6-sulfation at the GlcNAc residue (4), the sulfation of the C-6 position of GlcNAc is considered to be a de facto rate-limiting step in polylactosamine sulfation. Sulfation at the C-6 position of GlcNAc is involved in several important biological recognition phenomena including selectin-mediated cell adhesion (5-10), cell-to-cell interaction through siglecs (11)(12)(13)(14)(15), activation of CD44-mediated cellular interaction (16 -18), and dendritic cell function (19 -21).…”

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confidence: 99%

Significance of NF-κB/GATA Axis in Tumor Necrosis Factor-α-induced Expression of 6-Sulfated Cell Recognition Glycans in Human T-lymphocytes

Chen

Sakuma

Kannagi

2008

Journal of Biological Chemistry

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Sulfated glycans play critical roles in various cell recognition events among leukocytes. The 6-sulfated lactosamine glycans in particular have been widely noted for their importance because they are involved in cell recognition events mediated by celladhesion molecules such as selectins and sialic acid-recognizing molecules such as siglecs and also in the activation of CD44 in binding to extracellular matrix hyaluronate. A pro-inflammatory cytokine, tumor necrosis factor-␣, induces expression of 6-sulfated glycans on human leukocytes. Here we report that the transcription of the GlcNAc6ST-1 gene, the gene encoding a sulfotransferase for 6-sulfated glycan synthesis, is induced in human T-lymphoid cells through tandem NF-B and GATA motifs in its 5-regulatory region. Results of our reporter assays, immunoprecipitation, and chromatin immunoprecipitation analyses indicated that GATA-3 and/or GATA-2, but not GATA-1, associates with NF-B in a transcription factor complex on the 5-regulatory region of the gene and acts synergistically with NF-B in triggering GlcNAc6ST-1 transcription. Recently, a skin-homing subset of helper memory T cells exhibiting the Th2 marker CCR4 was shown to specifically express 6-sulfated glycans. The transactivation mechanism described here suggested that GlcNAc6ST-1 transcription is coordinated with the NF-B/GATA-3 axis, which is known to figure heavily in Th2 cell differentiation. In line with this, in vitro differentiation of human T cells to Th2 cells was found to significantly induce GlcNAc6ST-1 transcription and 6-sulfated glycan expression.

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“…2D). Other cell lines strongly expressing sialyl 6-sulfo Lewis x , such as a subclone of Namalwa cells (18) and SW480 cells transfected with 6-sulfotransferase cDNA (26), also failed to show statistically significant binding to siglec-9 (data not shown).…”

Section: Sialyl 6-sulfo Lewismentioning

confidence: 93%

Colonic Epithelial Cells Express Specific Ligands for Mucosal Macrophage Immunosuppressive Receptors Siglec-7 and -9

Miyazaki

Sakuma

Kawamura

et al. 2012

The Journal of Immunology

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Immune cells are known to express specific recognition molecules for cell surface glycans. However, mechanisms involved in glycan-mediated cell–cell interactions in mucosal immunity have largely been left unaccounted for. We found that several glycans preferentially expressed in nonmalignant colonic epithelial cells serve as ligands for sialic acid-binding Ig-like lectins (siglecs), the immunosuppressive carbohydrate-recognition receptors carried by immune cells. The siglec ligand glycans in normal colonic epithelial cells included disialyl Lewisa, which was found to have binding activity to both siglec-7 and -9, and sialyl 6-sulfo Lewisx, which exhibited significant binding to siglec-7. Expression of these siglec-7/-9 ligands was impaired upon carcinogenesis, and they were replaced by cancer-associated glycans sialyl Lewisa and sialyl Lewisx, which have no siglec ligand activity. When we characterized immune cells expressing siglecs in colonic lamina propriae by flow cytometry and confocal microscopy, the majority of colonic stromal immune cells expressing siglec-7/-9 turned out to be resident macrophages characterized by low expression of CD14/CD89 and high expression of CD68/CD163. A minor subpopulation of CD8+ T lymphocytes also expressed siglec-7/-9. Siglec-7/-9 ligation suppressed LPS-induced cyclooxygenase-2 expression and PGE2 production by macrophages. These results suggest that normal glycans of epithelial cells exert a suppressive effect on cyclooxygenase-2 expression by resident macrophages, thus maintaining immunological homeostasis in colonic mucosal membranes. Our results also imply that loss of immunosuppressive glycans by impaired glycosylation during colonic carcinogenesis enhances inflammatory mediator production.

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Human B-lymphocytes Express α2-6-Sialylated 6-Sulfo-N-acetyllactosamine Serving as a Preferred Ligand for CD22/Siglec-2

Cited by 74 publications

References 43 publications

In Situ trans Ligands of CD22 Identified by Glycan-Protein Photocross-linking-enabled Proteomics

In Situ trans Ligands of CD22 Identified by Glycan-Protein Photocross-linking-enabled Proteomics

Significance of NF-κB/GATA Axis in Tumor Necrosis Factor-α-induced Expression of 6-Sulfated Cell Recognition Glycans in Human T-lymphocytes

Colonic Epithelial Cells Express Specific Ligands for Mucosal Macrophage Immunosuppressive Receptors Siglec-7 and -9

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