清华大学祁海研究组报道，记忆B细胞的高可召回性需要ZFP318依赖的线粒体功能转录调控。该项研究成果发表在2024年6月17日出版的《免疫》上。

据悉，生发中心(GC)存在的记忆B细胞前体和记忆B细胞(MBCs)，诱导转录调节因子ZFP318的表达。

使用条件ZFP318荧光报告器，也可以消除表达ZFP318的细胞，研究团队发现表达ZFP318的记忆B细胞高度富集生发中心来源的细胞。虽然表达ZFP318的记忆B细胞仅占抗原特异性记忆B细胞群的一小部分，但它们的消除严重损害了召回反应。ZFP318的缺失没有改变初次反应的程度，但显著降低了记忆B细胞在再召回的参与。CD40连接促进ZFP318的表达，而B细胞受体(BCR)信号传导则受到抑制。

强制表达ZFP318增强了记忆B细胞的召回性能，否则反应较差。ZFP318缺陷的记忆B细胞表达较少的线粒体基因，线粒体结构受损，易受再激活诱导的细胞死亡的影响。表达ZFP318的记忆B细胞的丰度，而不是抗原特异性记忆B细胞的数量，与初免疫苗的效力相关。因此，ZFP318控制着记忆B细胞的可召回性，代表着体液免疫记忆的质量检查点。

附：英文原文

Title: High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

Author: Yifeng Wang, Wen Shao, Xin Liu, Qingtai Liang, Jiaqi Lei, Wenjuan Shi, Miao Mei, Ying Li, Xu Tan, Guocan Yu, Li Yu, Linqi Zhang, Hai Qi

Issue&Volume: 2024-06-17

Abstract: Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exitingmemory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescencereporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressingMBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constitutedonly a minority of the antigen-specific MBC compartment, their ablation severely impairedrecall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participationin recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficientMBCs expressed less mitochondrial genes, had structurally compromised mitochondria,and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressingMBCs, instead of the number of antigen-specific MBCs, correlated with the potencyof prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and representsa quality checkpoint of humoral immune memory.

DOI: 10.1016/j.immuni.2024.05.022

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00276-0