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

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-06-17 DOI:10.1016/j.immuni.2024.05.022
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
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Abstract

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

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记忆性 B 细胞的高可召回性需要 ZFP318 对线粒体功能的转录调控
转录调节因子ZFP318在生殖中心(GC)出苗期记忆B细胞前体和记忆B细胞(MBC)中被诱导表达。我们使用一种条件性 ZFP318 荧光报告器(该报告器也能消融 ZFP318 表达的细胞)发现,ZFP318 表达的 MBCs 高度富集于 GC 派生细胞中。虽然ZFP318表达的MBC只占抗原特异性MBC区系的少数,但它们的消减严重影响了回忆反应。Zfp318的缺失不会改变初级反应的程度,但会显著降低MBC参与回忆反应的程度。CD40 结扎可促进 Zfp318 的表达,而 B 细胞受体(BCR)信号转导则具有抑制作用。ZFP318的强制表达提高了MBC的回忆能力,否则它们的反应能力会很差。ZFP318缺陷的MBC表达的线粒体基因较少,线粒体结构受损,易受再激活诱导的细胞死亡影响。表达 ZFP318 的 MBC 的丰度(而不是抗原特异性 MBC 的数量)与原素增强疫苗的效力相关。因此,ZFP318控制着MBC的可召回性,是体液免疫记忆的质量检查点。
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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