Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11cCD80 cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.

中文翻译：

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I 型干扰素在慢性病毒感染中诱导表观遗传上独特的记忆 B 细胞亚群

记忆 B 细胞 (MBC) 是针对传染病的长期免疫力的关键提供者，但在慢性病毒感染中，它们不能产生有效的保护。慢性病毒感染如何破坏 MBC 的发展以及这种变化是否可逆仍然未知。通过在急性与慢性淋巴细胞性脉络丛脑膜炎病毒感染期间进行单细胞 (sc)ATAC-seq 和 scRNA-seq，我们确定了慢性感染期间富含干扰素 (IFN) 刺激基因 (ISG) 的记忆子集，该子集不同于 T-下注子集通常与慢性感染有关。感染早期阻断 IFNAR-1 改变了慢性 MBC 的染色质景观，降低了 ISG 诱导转录因子结合基序的可及性，并诱导主要 MBC 亚群的表型变化，其中 ISG 亚群减少，CD11cCD80 细胞增加。然而，时机至关重要，因为 MBC 在感染后 4 周对干预具有抵抗力。总之，我们的研究确定了在病毒感染期间指导 MBC 识别的关键机制。