Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
Cell Rep. 2022 Mar 15;38(11):110512. doi: 10.1016/j.celrep.2022.110512.
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.
生发中心（GCs）对于抗体亲和力成熟至关重要。与初始 B 细胞相比，GC B 细胞具有独特的细胞表面糖基化谱，但 GC 中糖基化变化的功能作用尚未确定。抗体 GL7 通过检测 GC，反映了 B 细胞受体的抑制共受体 CD22 的配体下调。为了检验 GC 中 CD22 配体下调的功能作用，我们构建了一种可维持 GC B 细胞上 CD22 配体的小鼠模型。利用该模型，我们证明了糖基化重塑在 GC 中 B 细胞的维持中起着关键作用。持续表达 CD22 配体可诱导 GC B 细胞中更高水平的细胞凋亡，减少记忆 B 细胞和浆细胞的产生，并延迟抗体亲和力成熟。这些缺陷依赖于 CD22，表明 B 细胞上 CD22 配体的下调在 GC 中发挥着关键作用。
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