Coordinated changes in glycosylation regulate the germinal center through CD22

Cell Rep. 2022 Mar 15;38(11):110512. doi: 10.1016/j.celrep.2022.110512.

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.

Keywords: B cell receptor; CD22; GL7; Siglec; antibodies; germinal center; glycosylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes
  • Germinal Center*
  • Glycosylation
  • Ligands
  • Mice
  • Polysaccharides / metabolism
  • Receptors, Antigen, B-Cell* / metabolism

Substances

  • Ligands
  • Polysaccharides
  • Receptors, Antigen, B-Cell