澳大利亚新南威尔士大学Stuart G. Tangye等研究人员合作发现，PD-1信号缺失的小鼠和人类中记忆B细胞和抗体反应的发育受损。2024年11月26日，《免疫》杂志在线发表了这项成果。

研究人员表示，T滤泡辅助（Tfh）细胞大量表达免疫受体程序性细胞死亡蛋白1（PD-1），且PD-1缺失对小鼠抗体（Ab）介导免疫的影响与Tfh细胞功能的损害相关。

研究人员重新探讨了PD-1-PD-L1轴在抗体介导免疫中的作用。具有遗传性PD-1或PD-L1缺失的个体具有较少的记忆B细胞和受损的抗体反应，类似于Pdcd1^−/−和Cd274^−/−Pdcd1lg2^−/−小鼠。PD-1、PD-L1或两者均可在体外激活后的人类初始B细胞表面被检测到。

缺失PD-1或PD-L1的B细胞在体内表现出转录调控因子c-Myc及其靶基因的表达减少，且PD-1缺失或中和PD-1或PD-L1抑制了人类B细胞中c-Myc的表达和抗体产生。此外，B细胞特异性删除Pdcd1可防止小鼠中记忆B细胞的生理积累。

因此，PD-1通过B细胞内在和外在机制，塑造了最佳的B细胞记忆和抗体介导免疫，这提示B细胞的失调可能在抗PD-1-PD-L1免疫疗法后，引发感染性和自身免疫并发症。

附：英文原文

Title: Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling

Author: Masato Ogishi, Koji Kitaoka, Kim L. Good-Jacobson, Darawan Rinchai, Baihao Zhang, Jun Wang, Vincent Gies, Geetha Rao, Tina Nguyen, Danielle T. Avery, Taushif Khan, Megan E. Smithmyer, Joseph Mackie, Rui Yang, Andrés Augusto Arias, Takaki Asano, Khoren Ponsin, Matthieu Chaldebas, Peng Zhang, Jessica N. Peel, Jonathan Bohlen, Romain Lévy, Simon J. Pelham, Wei-Te Lei, Ji Eun Han, Iris Fagniez, Maya Chrabieh, Candice Laine, David Langlais, Conor Gruber, Fatima Al Ali, Mahbuba Rahman, Caner Aytekin, Basilin Benson, Matthew J. Dufort, Clara Domingo-Vila, Kunihiko Moriya, Mark Shlomchik, Gulbu Uzel, Paul E. Gray, Daniel Suan, Kahn Preece, Ignatius Chua, Satoshi Okada, Shunsuke Chikuma, Hiroshi Kiyonari, Timothy I. Tree, Dusan Bogunovic, Philippe Gros, Nico Marr, Cate Speake, Richard A. Oram, Vivien Béziat, Jacinta Bustamante, Laurent Abel, Bertrand Boisson, Anne-Sophie Korganow, Cindy S. Ma

Issue&Volume: 2024-11-26

Abstract: 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.

DOI: 10.1016/j.immuni.2024.10.014

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00495-3