2009
DOI: 10.1073/pnas.0807207106
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Sialylated multivalent antigens engage CD22in transand inhibit B cell activation

Abstract: CD22 is an inhibitory coreceptor on the surface of B cells that attenuates B cell antigen receptor (BCR) signaling and, therefore, B cell activation. Elucidating the molecular mechanisms underlying the inhibitory activity of CD22 is complicated by the ubiquity of CD22 ligands. Although antigens can display CD22 ligands, the receptor is known to bind to sialylated glycoproteins on the cell surface. The propinquity of CD22 and cell-surface glycoprotein ligands has led to the conclusion that the inhibitory proper… Show more

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Cited by 121 publications
(188 citation statements)
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“…Moreover, the binding of immobilized epratuzumab to CD22 is distinctive from that of a synthetic a2,6-linked sialic acid, which efficiently prevented CD22 from co-capping and co-localization with BCR in the lipid rafts after BCR ligation. 40 Intriguingly, we did not observe any transient increase in intracellular calcium by immobilized epratuzumab in the Particulate-I format, but have noted a substantial decrease of antiIgM-induced mobilization of intracellular calcium in Daudi cells pretreated with either the Dried-I or the Wet-I format of epratuzumab for 1 h. These results are consistent with 2 previous findings: one reporting that a copolymer comprising multiple copies of 2, 4-dinitrophenyl (DNP) and a synthetic CD22 ligand (CD22L), which was capable of trans-binding to CD22 via colligation with BCR in a murine B cell line displaying a DNP-specific BCR, failed to induce any calcium flux; 41 the other reporting that preincubating B cells with the IgG or F (ab 0 ) 2 of epratuzumab reduced the amplitude of calcium mobilization stimulated by anti-IgM/IgG. 34 Thus, when both CD22 and BCR are co-clustered by immobilized epratuzumab or the DNP-CD22L copolymer, calcium signals resulting from BCR stimulation can be partially or completely suppressed, which is in contrast to the enhanced calcium flux found in B cells pretreated with certain anti-CD22 antibodies upon BCR activation, often attributed to sequestration of CD22 from BCR.…”
Section: Discussionsupporting
confidence: 91%
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“…Moreover, the binding of immobilized epratuzumab to CD22 is distinctive from that of a synthetic a2,6-linked sialic acid, which efficiently prevented CD22 from co-capping and co-localization with BCR in the lipid rafts after BCR ligation. 40 Intriguingly, we did not observe any transient increase in intracellular calcium by immobilized epratuzumab in the Particulate-I format, but have noted a substantial decrease of antiIgM-induced mobilization of intracellular calcium in Daudi cells pretreated with either the Dried-I or the Wet-I format of epratuzumab for 1 h. These results are consistent with 2 previous findings: one reporting that a copolymer comprising multiple copies of 2, 4-dinitrophenyl (DNP) and a synthetic CD22 ligand (CD22L), which was capable of trans-binding to CD22 via colligation with BCR in a murine B cell line displaying a DNP-specific BCR, failed to induce any calcium flux; 41 the other reporting that preincubating B cells with the IgG or F (ab 0 ) 2 of epratuzumab reduced the amplitude of calcium mobilization stimulated by anti-IgM/IgG. 34 Thus, when both CD22 and BCR are co-clustered by immobilized epratuzumab or the DNP-CD22L copolymer, calcium signals resulting from BCR stimulation can be partially or completely suppressed, which is in contrast to the enhanced calcium flux found in B cells pretreated with certain anti-CD22 antibodies upon BCR activation, often attributed to sequestration of CD22 from BCR.…”
Section: Discussionsupporting
confidence: 91%
“…Thus, besides the routine measurement of intracellular calcium as a marker for B-cell activation and cell surface binding to assess the affinity for CD22, the biological significance of CD22-targeting agents, particularly those derived from synthetic sialosides, 40,41,[45][46][47] should be substantiated with a suitable cytotoxicity assay, as exemplified by the capability of liposomal nanoparticles displaying both antigen and CD22L to induce antigen-specific B-cell apoptosis. 5 mg/mL; GAH, 10 mg/mL), and Wet-III (lane 7; hLL2, 7.5 mg/mL; GAH, 10 mg/mL; anti-IgM, 1 mg/mL).…”
Section: Discussionmentioning
confidence: 99%
“…The ability of CD22 to modulate B-cell responses by interacting in trans with glycosylated Ags has previously been demonstrated. 16 Here, we show that high concentrations of IVIg could act in a similar manner and reduce the strength of BCR-mediated signaling. This occurs through the CD22-SHP-1 inhibitory pathway and by downregulating calcium pathway activation, that determine the fate of B cells.…”
Section: Effect Of Ivig On Bcr-mediated Signaling Involves Cd22mentioning
confidence: 60%
“…Differences in the features of CPS-specific Ab response directed against whole S. pneumoniae, N. meningitidis, GBS, and S. suis cells can be explained first by differences in immunostimulatory properties intrinsic to CPS due to differences in the biochemistry of CPS (56), such as variations in the structure (57, 58), (60), and ability to bind to specific receptors (61)(62)(63). The presence of sialic acid may also have a potential impact as this sugar is well known to interfere with the immune system by molecular mimicry and inhibition of complement activation (64,65) and/or by interaction with the inhibitory CD22 receptor on B cells (66). It should be noted that in GBS CPS, sialic acid is ␣2,3 linked to adjacent galactose, but in S. suis, CPS is found in the ␣2,6 linkage (34).…”
Section: Discussionmentioning
confidence: 99%