T follicular helper (Tfh) cells abundantly express the immunoreceptor programmed cell death protein 1 (PD-1), and the impact of PD-1 deficiency on antibody (Ab)-mediated immunity in mice is associated with compromised Tfh cell functions. Here, we revisited the role of the PD-1-PD-L1 axis on Ab-mediated immunity. Individuals with inherited PD-1 or PD-L1 deficiency had fewer memory B cells and impaired Ab responses, similar to Pdcd1−/− and Cd274−/−Pdcd1lg2−/− mice. PD-1, PD-L1, or both could be detected on the surface of human naive B cells following in vitro activation. PD-1- or PD-L1-deficient B cells had reduced expression of the transcriptional regulator c-Myc and c-Myc-target genes in vivo, and PD-1 deficiency or neutralization of PD-1 or PD-L1 impeded c-Myc expression and Ab production in human B cells isolated in vitro. Furthermore, B cell-specific deletion of Pdcd1 prevented the physiological accumulation of memory B cells in mice. Thus, PD-1 shapes optimal B cell memory and Ab-mediated immunity through B cell-intrinsic and B cell-extrinsic mechanisms, suggesting that B cell dysregulation contributes to infectious and autoimmune complications following anti-PD-1-PD-L1 immunotherapy.

中文翻译：

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PD-1 信号转导缺陷的人和小鼠记忆 B 细胞发育和抗体反应受损


滤泡辅助性 T 细胞 （Tfh） 大量表达免疫受体程序性细胞死亡蛋白 1 （PD-1），PD-1 缺陷对小鼠抗体 （Ab） 介导的免疫的影响与 Tfh 细胞功能受损有关。在这里，我们重新审视了 PD-1-PD-L1 轴对 Ab 介导的免疫的作用。患有遗传性 PD-1 或 PD-L1 缺陷的个体具有较少的记忆 B 细胞和 Ab 反应受损，类似于 Pdcd1 - / - 和 Cd274 - / - Pdcd1lg2 - / - 小鼠。体外激活后，可以在人幼稚 B 细胞表面检测到 PD-1、PD-L1 或两者。PD-1 或 PD-L1 缺陷型 B 细胞在体内转录调节因子 c-Myc 和 c-Myc 靶基因的表达降低，PD-1 缺陷或 PD-1 或 PD-L1 的中和作用阻碍了体外分离 的人 B 细胞中 c-Myc 表达和 Ab 的产生。此外，Pdcd1 的 B 细胞特异性缺失阻止了小鼠记忆 B 细胞的生理积累。因此，PD-1 通过 B 细胞内源性和外源性机制塑造最佳 B 细胞记忆和 Ab 介导的免疫，表明 B 细胞失调导致抗 PD-1-PD-L1 免疫治疗后感染和自身免疫并发症。