The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans
The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans
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DOI：
10.1016/j.immuni.2020.03.020
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发表时间：
2020-05-19
期刊：
影响因子：
32.4
通讯作者：
Cancro, Michael P.
中科院分区：
文献类型：
--
作者：
Johnson, John L.;Rosenthal, Rebecca L.;Cancro, Michael P.
表达转录因子T-bet的B细胞亚群与体液免疫应答和自身免疫相关。在此，我们研究了流感特异性免疫应答背景下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细胞出现在生发中心，获得记忆B细胞标志物，并无限期持续。谱系追踪和IgH库分析显示T-bet（-）和T-bet（+）MBC之间的相互转化最小，并且寄生虫显示出不同的组织驻留和再循环特性。T-bet（+）MBC可分为再循环T-bet（lo）MBC和脾驻留T-bet（hi）MBC。人类MBC显示出类似的特征。条件性基因缺失研究显示，T-bet在B细胞中的表达是几乎所有HA茎特异性IgG 2c抗体和持久的流感中和滴度所必需的。因此，T-bet表达区分MBC子集，其具有深刻不同的归巢、驻留和功能特性，并且介导体液免疫记忆的不同方面。
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(lo) MBCs and spleen-resident T-bet(hi) 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.