Coordinated changes in glycosylation regulate the germinal center through CD22

Germinal centers (GCs) are essential for antibody affinity maturation. GC B cells have a unique repertoire of cell surface glycans compared with naive B cells, yet functional roles for changes in glycosylation in the GC have yet to be ascribed. Detection of GCs by the antibody GL7 reflects a downregulation in ligands for CD22, an inhibitory co-receptor of the B cell receptor. To test a functional role for downregulation of CD22 ligands in the GC, we generate a mouse model that maintains CD22 ligands on GC B cells. With this model, we demonstrate that glycan remodeling plays a critical role in the maintenance of B cells in the GC. Sustained expression of CD22 ligands induces higher levels of apoptosis in GC B cells, reduces memory B cell and plasma cell output, and delays affinity maturation of antibodies. These defects are CD22 dependent, demonstrating that downregulation of CD22 ligands on B cells plays a critical function in the GC. [Display omitted] •A mouse model (CMAHON) is made to test a role for altered glycosylation in the GC•CMAHON display a CD22-dependent defective GC response•Altered glycosylation in the GC affects the ability of CD22 to regulate the BCR•Altered glycosylation/CD22 play a role in antigen processing, survival, and selection Changes in glycosylation on GC B cells are hypothesized to affect CD22, an inhibitory BCR co-receptor. Enterina et al. show that altered glycosylation in the GC leads to a CD22-dependent defective GC. Therefore, coordinated changes in glycosylation in the GC play a critical functional role through modulating the function of CD22.