B Lymphocyte Biology Lab, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Genomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
EMBO Rep. 2022 Dec 6;23(12):e55000. doi: 10.15252/embr.202255000. Epub 2022 Oct 7.
Germinal centers (GC) are microstructures where B cells that have been activated by antigen can improve the affinity of their B cell receptors and differentiate into memory B cells (MBCs) or antibody-secreting plasma cells. Here, we have addressed the role of activation-induced deaminase (AID), which initiates somatic hypermutation and class switch recombination, in the terminal differentiation of GC B cells. By combining single cell transcriptome and immunoglobulin clonal analysis in a mouse model that traces AID-experienced cells, we have identified a novel subset of late-prePB cells (L-prePB), which shares the strongest clonal relationships with plasmablasts (PBs). Mice lacking AID have various alterations in the size and expression profiles of transcriptional clusters. We find that AID deficiency leads to a reduced proportion of L-prePB cells and severely impairs transitions between the L-prePB and the PB subsets. Thus, AID shapes the differentiation fate of GC B cells by enabling PB generation from a prePB state.
生发中心（GC）是微结构，其中被抗原激活的 B 细胞可以提高其 B 细胞受体的亲和力，并分化为记忆 B 细胞（MBC）或分泌抗体的浆细胞。在这里，我们研究了起始体细胞高频突变和类别转换重组的激活诱导脱氨酶（AID）在 GC B 细胞终末分化中的作用。通过在一种可以追踪 AID 经历细胞的小鼠模型中结合单细胞转录组和免疫球蛋白克隆分析，我们鉴定出一种新型晚期 pre-PB 细胞（L-prePB）亚群，该亚群与浆母细胞（PBs）具有最强的克隆关系。缺乏 AID 的小鼠在转录簇的大小和表达谱上有各种改变。我们发现 AID 缺乏导致 L-prePB 细胞比例减少，并严重损害 L-prePB 和 PB 亚群之间的转换。因此，AID 通过使 PB 从 prePB 状态产生，从而塑造 GC B 细胞的分化命运。
