Coordinated changes in glycosylation regulate the germinal centre through CD22
Coordinated changes in glycosylation regulate the germinal centre through CD22
Abstract Germinal centres (GC) are sites of B-cell expansion and selection, which are essential for antibody affinity maturation. Compared to naive follicular B-cells, GC B-cells have several notable changes in their cell surface glycans. While these changes are routinely used to identify the GC, functional roles for these changes have yet to be ascribed. Detection of GCs by the antibody GL7 reflects a reduction in the glycan ligands for CD22, which is an inhibitory co-receptor of the B-cell receptor (BCR). To test a functional role for downregulated CD22 ligands in the GC, we generated a mouse model that maintains CD22 ligands on GC B-cells. With this model, we demonstrate that glycan remodeling is crucial for proper GC B-cell response, including plasma cell output and affinity maturation of antibodies. The defect we observe in this model is dependent on CD22, highlighting that coordinated downregulation of CD22 ligands on B cells plays a critical function in the GC. Collectively, our study uncovers a crucial role for glycan remodeling and CD22 in B-cell fitness in the GC.
Sarkar Susmita、Jung Jaesoo、Takematsu Hiromu、Nitschke Lars、Shlomchick Mark J.、Arlian Britni M.、Macauley Matthew S.、Baldwin Troy A.、Enterina Jhon R.、Xiao Changchun、Streith Laura、Paulson James C.、Meyer Sarah J.
Department of Chemistry, University of AlbertaDepartment of Chemistry, University of AlbertaDepartment of Human Health Sciences, Graduate School of Medicine, Kyoto UniversityDivision of Genetics, Department of Biology, University of ErlangenDepartment of Immunology, University of Pittsburgh School of MedicineDepartment of Molecular Medicine, The Scripps Research InstituteDepartment of Medical Microbiology and Immunology, University of Alberta||Department of Chemistry, University of AlbertaDepartment of Medical Microbiology and Immunology, University of AlbertaDepartment of Medical Microbiology and Immunology, University of AlbertaDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Medical Microbiology and Immunology, University of AlbertaDepartment of Molecular Medicine, The Scripps Research InstituteDivision of Genetics, Department of Biology, University of Erlangen
基础医学分子生物学生物化学
Sarkar Susmita,Jung Jaesoo,Takematsu Hiromu,Nitschke Lars,Shlomchick Mark J.,Arlian Britni M.,Macauley Matthew S.,Baldwin Troy A.,Enterina Jhon R.,Xiao Changchun,Streith Laura,Paulson James C.,Meyer Sarah J..Coordinated changes in glycosylation regulate the germinal centre through CD22[EB/OL].(2025-03-28)[2025-05-22].https://www.biorxiv.org/content/10.1101/2021.04.30.442136.点此复制
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