CD22, a B cell-specific immunoglobulin superfamily member, is a sialic acid-binding lectin.

D Sgroi,A Varki,S Braesch-Andersen,I Stamenkovic

doi:10.1016/s0021-9258(18)53139-2

D Sgroi, A Varki + Show 2 more

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https://doi.org/10.1016/s0021-9258(18)53139-2

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Abstract

The B lymphocyte cell surface receptor CD22 is an adhesion molecule that can mediate binding to several leukocyte subsets. The first CD22 ligand to be identified was the receptor-linked phosphotyrosine phosphatase CD45, but several lines of evidence suggest that CD22 may interact with multiple counter receptors on adjacent lymphocytes. In the present work, we show that in addition to CD45, a soluble CD22-immunoglobulin fusion protein (CD22Rg) recognizes several other distinct lymphocyte sialoglycoproteins. CD22-mediated adhesion is dependent upon the presence of sialic acids on ligands. CD22Rg is observed to bind specifically to a 115-kDa sialoglycoprotein in COS cells transfected with an alpha-2,6-sialyltransferase cDNA, but not in COS cells transfected with unrelated cDNA clones, indicating that at least some CD22-mediated interactions require presentation of sialic acid in an alpha-2,6 linkage by CD22 ligands. In all cases, truncation of the side chain of sialic acids by mild periodate oxidation abolishes recognition by CD22Rg. Direct binding of CD22Rg to lymphoid cells also requires sialic acids and their side chains. Taken together, these observations indicate that CD22 is a sialic acid-binding lectin and may define a novel functional subset of immunoglobulin superfamily adhesion molecules.

Highlights

Cell-cell adhesion plays a critical role in the normal function of the immune system, regulating lymphocyte response to antigenic challenge, recirculation to lymphoid tissues, and the extravasation of responder cells to sites of injury
CD22 is a B cell lineage-restricted cell surface glycoprotein belonging to the immunoglobulin gene superfamily andis highly homologous to several adhesion molecules, including myelin-associatedglycoprotein(MAG)’ (Lai et al, 1987), neural cell adhesion molecule (NCAM) (Cunningham et al, 1 9 8 7 )a, n dt h e vascular adhesion molecule V-CAM/In
CD22-immunoglobulin fusion protein, termed CD22Rg, was developed (Stamenkovic et al, 1991)comprising the first three centrifugation for 10 min, and lysates were precleared with human CD22 Ig domains, linked to human IgG Fc regions (Fig. 1)

Summary

We have reported previously that a recombinant soluble

The abbreviations used are: MAG, myelin-associated glycoprotein; NCAM, neural cell adhesion molecule;Rg, receptor-globulin; FBS, fetal bovine serum; mAb, monoclonal antibody; PBS, phosphate-buffered saline; PHA, phytohemagglutinin. Phytohemagglutinin (PHA) blasts, T and Bcell lines were washed in ice-cold PBS, resuspended in PBS with 2 mM sodium periodate at 1X lo6cells/ml, and incubated on ice in the dark for 15min (Van Lenten and Ashwell, 1971;Gahmberg and Anderson, the present study we show that soluble CD22P recognizes 1977).Cells were washed in ice-coldPBS andwere stained with either multiple glycoprotein ligands on B and T cells, as well as a major 115-kDa sialoglycoprotein on a-2,6-sialyltransferasetransfected COS cells, and thatCD22P-mediated adhesion is dependent upon the presenceof sialic acid sidechain residues on the ligands. Immediately neutralized with 1M Tris to a final pH of 7.5, dialyzed overnight against PBS,and the proteinconcentrationdetermined using a Bio-Rad protein assay kit

RESULTS

CEM cells

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