B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet+ and T-bet- memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet- and T-bet+ hemagglutinin (HA)-specific B cells arose in germinal centers, acquired memory B cell markers, and persisted indefinitely. Lineage tracing and IgH repertoire analyses revealed minimal interconversion between T-bet- and T-bet+ MBCs, and parabionts showed differential tissue residency and recirculation properties. T-bet+ MBCs could be subdivided into recirculating T-betlo MBCs and spleen-resident T-bethi MBCs. Human MBCs displayed similar features. Conditional gene deletion studies revealed that T-bet expression in B cells was required for nearly all HA stalk-specific IgG2c antibodies and for durable neutralizing titers to influenza. Thus, T-bet expression distinguishes MBC subsets that have profoundly different homing, residency, and functional properties, and mediate distinct aspects of humoral immune memory.

中文翻译：

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转录因子 T-bet 解决了小鼠和人类中具有不同组织分布和抗体特异性的记忆 B 细胞亚群。

表达转录因子 T-bet 的 B 细胞亚群与体液免疫反应和自身免疫有关。在这里，我们在流感特异性免疫反应的背景下检查了 T-bet+ 和 T-bet- 记忆 B 细胞 (MBC) 的解剖分布、克隆关系和功能特性。在小鼠中，T-bet 和 T-bet+ 血凝素 (HA) 特异性 B 细胞均出现在生发中心，获得记忆 B 细胞标记，并无限期地持续存在。谱系追踪和 IgH 曲目分析显示 T-bet- 和 T-bet+ MBCs 之间的相互转换最小，并且 parabionts 显示出不同的组织驻留和再循环特性。T-bet+ MBCs 可细分为循环 T-betlo MBCs 和脾常驻 T-bethi MBCs。人类 MBC 表现出相似的特征。条件性基因缺失研究表明，几乎所有 HA 茎特异性 IgG2c 抗体和对流感的持久中和滴度都需要 B 细胞中的 T-bet 表达。因此，T-bet 表达区分 MBC 亚群，这些亚群具有截然不同的归巢、驻留和功能特性，并介导体液免疫记忆的不同方面。