澳大利亚莫纳什大学Kim L. Good-Jacobson团队近期取得重要工作进展，他们研究提出，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。相关研究成果2024年4月8日在线发表于《免疫》杂志上。

据介绍，记忆B细胞（MBC）是抵抗传染病的长期免疫的关键提供者，但在慢性病毒感染中，它们不能产生有效的保护作用。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不得而知。

通过急性和慢性淋巴细胞性脉络膜脑膜炎病毒感染期间的scATAC-seq和scRNA-seq，研究人员确定了慢性感染期间富含干扰素（IFN）刺激基因（ISG）的记忆亚群，该亚群与通常与慢性感染相关的T-bet⁺亚群不同。在感染早期阻断IFNAR-1可改变慢性MBC的染色质结构，降低了ISG诱导的转录因子结合基序的可及性，并诱导优势MBC亚群发生表型变化，ISG亚群减少，CD11c⁺CD80⁺细胞增加。然而，时机至关重要，MBC在感染后4周对干预具有抵抗力。

总之，这一研究确定了在病毒感染期间指导MBC识别的关键机制。

附：英文原文

Title: Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection

Author: Lucy Cooper, Hui Xu, Jack Polmear, Liam Kealy, Christopher Szeto, Ee Shan Pang, Mansi Gupta, Alana Kirn, Justin J. Taylor, Katherine J.L. Jackson, Benjamin J. Broomfield, Angela Nguyen, Catarina Gago da Graa, Nicole La Gruta, Daniel T. Utzschneider, Joanna R. Groom, Luciano Martelotto, Ian A. Parish, Meredith O’Keeffe, Christopher D. Scharer, Stephanie Gras, Kim L. Good-Jacobson

Issue&Volume: 2024-04-08

Abstract: Memory B cells (MBCs) are key providers of long-lived immunity against infectiousdisease, yet in chronic viral infection, they do not produce effective protection.How chronic viral infection disrupts MBC development and whether such changes arereversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acuteversus chronic lymphocytic choriomeningitis viral infection, we identified a memorysubset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infectionthat was distinct from the T-bet+ subset normally associated with chronic infection. Blockade of IFNAR-1 early in infectiontransformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducingtranscription factor binding motifs and inducing phenotypic changes in the dominatingMBC subset, with a decrease in the ISG subset and an increase in CD11c+CD80+ cells. However, timing was critical, with MBCs resistant to intervention at 4 weekspost-infection. Together, our research identifies a key mechanism to instruct MBCidentity during viral infection.

DOI: 10.1016/j.immuni.2024.03.016

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00137-7