Methyltransferase Nsd2 Ensures Germinal Center Selection by Promoting Adhesive Interactions between B Cells and Follicular Dendritic Cells
Methyltransferase Nsd2 Ensures Germinal Center Selection by Promoting Adhesive Interactions between B Cells and Follicular Dendritic Cells
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甲基转移酶 Nsd2 通过促进 B 细胞和滤泡树突细胞之间的粘附相互作用确保生发中心选择
DOI：
10.1016/j.celrep.2018.11.096
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发表时间：
2018-12-18
期刊：
影响因子：
8.8
通讯作者：
Wang, Xiaoming
中科院分区：
文献类型：
--
作者：
Chen, Jingjing;Li, Ni;Wang, Xiaoming
抗体亲和力成熟是B细胞基于抗原的选择过程，发生在生发中心(GC)。GCB细胞必须有效地识别、获取和呈递滤泡树突状细胞(FDCs)的抗原，才能从T辅助细胞接收阳性选择信号。以前的研究表明，GCB细胞与FDCs发生黏附作用，但细胞黏附的调控机制及其功能相关性尚不清楚。在这里，我们确定H3K36me2甲基转移酶Nsd2是GCB细胞-FDC黏附的关键调节因子。NSD2缺失轻度降低了GC应答，但强烈损害了B细胞亲和力成熟。在机制上，Nsd2直接调控GCB细胞中多种肌动蛋白聚合相关基因的表达。NSD2缺失减少了B细胞与FDC表达的黏附分子的黏附，从而影响B细胞受体(BCR)信号转导和抗原获取。总体而言，Nsd2通过增强BCR信号和T细胞帮助来协调GCB阳性选择。
Antibody affinity maturation, which is an antigen-based selection process for B cells, occurs in germinal centers (GCs). GCB cells must efficiently recognize, acquire, and present antigens from follicular dendritic cells (FDCs) to receive positive selection signals from T helper cells. Previous studies showed that GCB cells undergo adhesive interactions with FDCs, but the regulatory mechanisms underlying the cell adhesions and their functional relevance remain unclear. Here, we identified H3K36me2 methyltransferase Nsd2 as a critical regulator of GCB cell-FDC adhesion. Nsd2 deletion modestly reduced GC responses but strongly impaired B cell affinity maturation. Mechanistically, Nsd2 directly regulated expression of multiple actin polymerization-related genes in GCB cells. Nsd2 loss reduced B cell adhesion to FDC-expressed adhesion molecules, thus affecting both B cell receptor (BCR) signaling and antigen acquisition. Overall, Nsd2 coordinates GCB positive selection by enhancing both BCR signaling and T cell help.