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The PD-1 Regulatory Axis Inhibits T Cell–Independent B Cell Memory Generation and Reactivation
The Journal of Immunology ( IF 3.6 ) Pub Date : 2021-10-15 , DOI: 10.4049/jimmunol.2100336
M. Ariel Spurrier 1 , Jamie E. Jennings-Gee 1 , Christina A. Daly 1 , Karen M. Haas 1
Affiliation  

The inability of T cell–independent type 2 (TI-2) Ags to induce recall responses is a poorly understood facet of humoral immunity, yet critically important for improving vaccines. Using normal and VHB1–8 transgenic mice, we demonstrate that B cell–intrinsic PD-1 expression negatively regulates TI-2 memory B cell (Bmem) generation and reactivation in part through interacting with PDL1 and PDL2 on non–Ag-specific cells. We also identified a significant role for PDL2 expression on Bmems in inhibiting reactivation and Ab production, thereby revealing a novel self-regulatory mechanism exists for TI-2 Bmems. This regulation impacts responses to clinically relevant vaccines, because PD-1 deficiency was associated with significantly increased Ab boosting to the pneumococcal vaccine after both vaccination and infection. Notably, we found a B cell–activating adjuvant enabled even greater boosting of protective pneumococcal polysaccharide-specific IgG responses when PD-1 inhibition was relieved. This work highlights unique self-regulation by TI-2 Bmems and reveals new opportunities for significantly improving TI-2 Ag-based vaccine responses.



中文翻译:

PD-1 调节轴抑制独立于 T 细胞的 B 细胞记忆生成和再激活

不依赖 T 细胞的 2 型 (TI-2) Ags 无法诱导回忆反应是体液免疫的一个知之甚少的方面,但对于改进疫苗至关重要。使用正常和 V H B1-8 转基因小鼠,我们证明 B 细胞内在 PD-1 表达负调节 TI-2 记忆 B 细胞 (B mem ) 的产生和重新激活,部分是通过与非银上的 PDL1 和 PDL2 相互作用。特定细胞。我们还确定了 B mems上 PDL2 表达在抑制再激活和 Ab 产生方面的重要作用,从而揭示了 TI-2 B mems存在的一种新的自我调节机制. 这一规定会影响对临床相关疫苗的反应,因为 PD-1 缺乏与疫苗接种和感染后肺炎球菌疫苗的 Ab 增强显着增加有关。值得注意的是,我们发现当 PD-1 抑制解除时,B 细胞激活佐剂能够更大程度地增强保护性肺炎球菌多糖特异性 IgG 反应。这项工作突出了 TI-2 B mems独特的自我调节,并揭示了显着改善基于 TI-2 Ag 的疫苗反应的新机会。

更新日期:2021-10-06
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