Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Immunity. 2020 May 19;52(5):842-855.e6. doi: 10.1016/j.immuni.2020.03.020. Epub 2020 Apr 29.
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-bet MBCs and spleen-resident T-bet 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.
B 细胞亚群表达转录因子 T-bet 与体液免疫反应和自身免疫有关。在这里,我们研究了流感特异性免疫反应背景下 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 细胞均在生发中心中出现,获得了记忆 B 细胞标志物,并无限期持续存在。谱系追踪和 IgH 库分析显示 T-bet 和 T-bet MBC 之间几乎没有相互转换,而联体动物显示出不同的组织驻留和再循环特性。T-bet MBC 可进一步分为循环 T-bet MBC 和脾脏驻留 T-bet MBC。人类 MBC 表现出类似的特征。条件基因缺失研究表明,B 细胞中 T-bet 的表达几乎是所有 HA 茎特异性 IgG2c 抗体和流感病毒持久中和滴度所必需的。因此,T-bet 的表达区分了具有截然不同归巢、驻留和功能特性的 MBC 亚群,并介导了体液免疫记忆的不同方面。