Diacylglycerol kinases (DGKs) limit antigen receptor signaling in immune cells by consuming the second messenger diacylglycerol (DAG) to generate phosphatidic acid (PA). Here, we showed that DGKζ promotes lymphocyte function–associated antigen 1 (LFA-1)–mediated adhesion and F-actin generation at the immune synapse of B cells with antigen-presenting cells (APCs), mostly in a PA-dependent manner. Measurement of single-cell mechanical force generation indicated that DGKζ-deficient B cells exerted lower forces at the immune synapse than did wild-type B cells. Nonmuscle myosin activation and translocation of the microtubule-organizing center (MTOC) to the immune synapse were also impaired in DGKζ-deficient B cells. These functional defects correlated with the decreased ability of B cells to present antigen and activate T cells in vitro. The in vivo germinal center response of DGKζ-deficient B cells was also reduced compared with that of wild-type B cells, indicating that loss of DGKζ in B cells impaired T cell help. Together, our data suggest that DGKζ shapes B cell responses by regulating actin remodeling, force generation, and antigen uptake–related events at the immune synapse. Hence, an appropriate balance in the amounts of DAG and PA is required for optimal B cell function.

二酰基甘油激酶 (DGK) 通过消耗第二信使二酰基甘油 (DAG) 产生磷脂酸 (PA) 来限制免疫细胞中的抗原受体信号传导。在这里，我们发现 DGKζ 促进淋巴细胞功能相关抗原 1 (LFA-1) 介导的粘附和 F-肌动蛋白在 B 细胞与抗原呈递细胞 (APC) 的免疫突触中的生成，主要以 PA 依赖性方式。单细胞机械力产生的测量表明，DGKζ 缺陷型 B 细胞对免疫突触施加的力低于野生型 B 细胞。在 DGKζ 缺陷的 B 细胞中，非肌肉肌球蛋白激活和微管组织中心 (MTOC) 向免疫突触的易位也受到损害。这些功能缺陷与 B 细胞在体外呈递抗原和激活 T 细胞的能力下降有关。与野生型 B 细胞相比，DGKζ 缺陷型 B 细胞的体内生发中心反应也降低，表明 B 细胞中 DGKζ 的缺失损害了 T 细胞的帮助。总之，我们的数据表明 DGKζ 通过调节免疫突触的肌动蛋白重塑、力产生和抗原摄取相关事件来塑造 B 细胞反应。因此，最佳 B 细胞功能需要 DAG 和 PA 量的适当平衡。