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.

Selective augmentation of intestinal immunity by CD22-dependent SHP-1 control of β7integrin expression

“…Mechanistically, we found that, in addition to the ITIM docking motifs in the cytoplasmic tail, the lectin-carbohydrate binding activity of CD22 also contributes to α 4 β 7 regulation, although the reduction of α 4 β 7 levels on B cells, and the inhibition of PP homing were less dramatic in the lectin mutant than with ITIM deficiency. On B cells, CD22 associates in cis with α2-6 Sia modified membrane proteins including CD22 itself and CD45: these cis-interactions can bring ITIMbound SHP-1 phosphatase in close proximity to target substrates, altering the phosphorylation state and function of associated molecules (Enterina et al, 2019;Meyer et al, 2018). Using a biotin-tyramide-based proximity labeling method (Alborzian Deh Sheikh et al, 2018) to label molecules in close proximity to CD22, we reproduced the finding that CD45 and CD22 are α2-6 Siadependent CD22 cis-ligands, but we did not detect interaction with α 4 β 7 (data not shown), suggesting either that, such interactions are transient (Collins et al, 2004) or that CD22 acts through intermediate signaling molecules to regulate α 4 β 7 .…”

Development of Recombinant Immunotoxins for Hairy Cell Leukemia

“…CD22, also called Siglec 2, is expressed mainly by B-lymphocytes and functions to inhibit B-cell receptor signaling [ 107 , 108 ]. The rationale for the development of a CD22 recombinant immunotoxin was based on characteristics of both HCL and non-HCL hematologic malignancies.…”

The many (sur)faces of B cells

“…During embryonic development, different waves of progenitors from various sites of origin give raise to different B cell progenies [3], while B cell maturation in turn is fine-tuned and controlled by different populations of T follicular cells [4]. CD22 binding to glycans ensures self-tolerance [5] and several subsets of B lymphocytes exert themselves immunosuppressive functions [6].…”

“…Enterina et al. focus on one particular element in the arsenal of tools meant to keep them at bay, a co-receptor found on B cells named CD22, which antagonises BCR signalling [5]. Much conveniently, the patterns of cell surface glycosylation differ markedly between vertebrates and pathogens.…”