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.
摘要：
转录调节因子ZFP318的表达在生发中心(GC)-离开的记忆B细胞前体和记忆B细胞(MBC)中被诱导。使用条件ZFP318荧光报告子，也能够消除ZFP318表达细胞，我们发现表达ZFP318的MBC高度富含GC来源的细胞。尽管表达ZFP318的MBC仅构成抗原特异性MBC区室的一小部分，他们的消融严重受损的回忆反应。Zfp318的缺失不会改变主要响应的大小，但会显着降低MBC在回忆中的参与。CD40连接促进Zfp318表达，而B细胞受体（BCR）信号是抑制性的。强制ZFP318表达增强了反应不佳的MBC的回忆性能。ZFP318缺陷型MBC表达较少的线粒体基因，线粒体结构受损，并且易受再激活诱导的细胞死亡的影响。表达ZFP318的MBCs的丰度，而不是抗原特异性MBCs的数量，与初免疫苗的效力相关。因此,ZFP318控制MBC可重现性,并且代表体液免疫记忆的质量检查点。
