CD22 is Indispensable for Galectin-9-mediated Inhibition of B Cell Signaling

B-cells are an important component of the adaptive immune system, producing antibodies and conferring long-term immunity. B-cell activation is initiated by recognition of foreign particles (antigens) by B-cell receptors (BCR). Previous research in our lab found that the lectin, Galectin-9 (Gal9), regulates B-cell activation; however, the mechanism remains unclear. In this study, we demonstrate using super-resolution microscopy that Gal9 regulates the organization of a lattice of inhibitory and stimulatory receptors to inhibit B-cell signaling. We found that the inhibitory receptor CD22 is crucial for this Gal9-mediated mechanism. Furthermore, we demonstrate that CD22 N-linked glycosylation is required for Gal9-mediated inhibition of signaling. To our knowledge, our study is the first to highlight the importance of galectins in regulating CD22 organization, as well as define N-glycans in CD22 as imperative in regulating B-cell signaling. Our findings may have important implications for the therapeutic application of Gal9 to alleviate B-cell mediated autoimmune diseases.M.Sc