GSE196206
Transcriptome analysis of mouse WT and CD22 KO GC B cells
Germinal centres (GC) are specialized sites where B cells expand and diversify their antibody genes through somatic hypermutation. GC B-cells are routinely identified through distinct changes on their surface carbohydrates, known as glycans. One striking modification relates to the monosaccharide sialic acid. In mice, this change is mediated through downregulation of an enzyme called CMAH, which results in a GC-specific loss of preferred ligand for CD22, a member of the sialic acid-binding immunoglobulin-type lectins (Siglecs) and an inhibitory co-receptor of the B-cell antigen receptor (BCR). Here, we identified that glycan remodeling, mediated by downregulation of CMAH, is crucial for the GC B-cell response, and production of memory B-cells, plasma cells, and high affinity antibodies. We also demonstrated that the function of these altered glycans is dependent on CD22, highlighting that coordinated loss of preferred ligands acts to modulates the CD22 activity in the GC B-cells. Overall, our study reveals that intrinsic glycan remodeling functions to optimize the B-cell responses in the GC by controlling CD22. Overall design: WT and CD22 KO mice were immunized with chicken ovalbumin-displaying liposomes. Dark zone (B220+CD19+IgD-GL7+CXCR4highCD86low) and light zone (B220+CD19+IgD-GL7+CXCR4lowCD86high) sorted from splenocytes of mice, at day 14 post-immunization. RNA was isolated and processed for next-generation RNA sequencing.