Sialylated multivalent antigens engage CD22in transand inhibit B cell activation

Abstract

Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation Adam H. Courtneya, Erik B. Puffera, Jason K. Pontrellob, Zhi-Qiang Yangb, and Laura L. Kiesslinga,b,1 Departments of aBiochemistry and bChemistry, University of Wisconsin, Madison, WI 53706 Edited by Carolyn R. Bertozzi, University of California, Berkeley, CA, and approved December 29, 2008 (received for review July 24, 2008) 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 properties of the receptor are due to cis interactions. Here, we examine the functional consequences of trans interactions by employing sialy- lated multivalent antigens that can engage both CD22 and the BCR. Exposure of B cells to sialylated antigens results in the inhibition of key steps in BCR signaling. These results reveal that antigens bearing CD22 ligands are powerful suppressors of B cell activation. The ability of sialylated antigens to inhibit BCR signaling through trans CD22 interactions reveals a previously unrecognized role for the Siglec-family of receptors as modulators of immune signaling. B cell antigen receptor
multivalency
sialic acid
siglec
autoimmunity T he initiation of an immune response or the prevention of autoimmunity depends upon the ability of the B cell antigen receptor (BCR) to transmit signals that positively or negatively regulate B lymphocyte survival, proliferation, and differentiation (1). To avoid detrimental autoimmune responses, a means of differentiating between foreign and self-antigens is required; co- receptors tha

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