Coordinated roles for glycans in regulating the inhibitory function of CD22 on B cells

Abstract CD22 is an inhibitory B cell co-receptor that recognizes sialic acid-containing glycoconjugates as ligands. Interactions with its glycan ligands are key to regulating the ability of CD22 to modulate B cell function, the most widely explored of which is antagonizing B cell receptor (BCR) signaling. Most importantly, interactions of CD22 with ligands on the same cell (cis) control the organization of CD22 on the cell surface, which minimizes co-localization with the BCR. In contrast with the modest ability of CD22 to intrinsically dampen BCR signaling, glycan ligands presented on another cell (trans) along with an antigen drawn CD22 and the BCR together within an immunological synapse, strongly inhibiting BCR signaling. New concepts are emerging for how CD22 controls B cell function, such as changes in glycosylation at different stages of B cell differentiation, specifically on GC B cells. Related to these changes, new players, such galectin-9, have been discovered that regulate cell surface nanoclusters of CD22. Roles of glycan ligands in controlling CD22 are the primary focus of this review as we highlight the ability of CD22 to modulate B cell function.