Coordinated changes in glycosylation regulate the germinal center through CD22
Jhon R. Enterina, Susmita Sarkar, Laura Streith, Jaesoo Jung, Britni M. Arlian, Sarah J. Meyer, Hiromu Takematsu, Changchun Xiao, Troy A. Baldwin, Lars Nitschke, Mark J. Shlomchik, James C. Paulson, Matthew S. Macauley
Abstract
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.