Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers.
Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers.
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DOI：
10.2139/ssrn.3825161
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发表时间：
2021-04
期刊：
影响因子：
32.4
通讯作者：
Wenzhi Song;Olivia Q. Antao;E. Condiff;G. M. Sanchez;I. Chernova;K. Zembrzuski;H. Steach;K. Rubtsova
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文献类型：
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作者：
Wenzhi Song;Olivia Q. Antao;E. Condiff;G. M. Sanchez;I. Chernova;K. Zembrzuski;H. Steach;K. Rubtsova
Tbet+ CD 11 c + B细胞在小鼠和人的1型病原体攻击、衰老和自身免疫过程中产生。在这里，我们检查了这个B细胞亚群的发育要求。在急性感染中，辅助性T滤泡（Tfh）细胞，而不是Th 1细胞，通过近端递送帮助驱动Tbet+ CD 11 c + B细胞生成。Tbet+ CD 11 c + B细胞在生发中心（GC）形成之前发育，表现出与GC B细胞不同的表型和转录谱。命运追踪显示，大多数Tbet+ CD 11 c + B细胞的发育独立于GC进入和细胞内在Bcl 6表达。Tbet+ CD 11 c+和GC B细胞表现出最小的库重叠，表明不同的发育途径。随着感染消退，Tbet+ CD 11 c + B细胞定位于脾滞留依赖于整联蛋白LFA-1和VLA-4的边缘区，形成竞争性记忆亚群，有助于再激发时抗体产生和二次GC接种。因此，Tbet+ CD 11 c + B细胞包含能够快速和稳健回忆应答的GC非依赖性记忆亚群。
Tbet+CD11c+ B cells arise during type 1 pathogen challenge, aging, and autoimmunity in mice and humans. Here, we examined the developmental requirements of this B cell subset. In acute infection, T follicular helper (Tfh) cells, but not Th1 cells, drove Tbet+CD11c+ B cell generation through proximal delivery of help. Tbet+CD11c+ B cells developed prior to germinal center (GC) formation, exhibiting phenotypic and transcriptional profiles distinct from GC B cells. Fate tracking revealed that most Tbet+CD11c+ B cells developed independently of GC entry and cell-intrinsic Bcl6 expression. Tbet+CD11c+ and GC B cells exhibited minimal repertoire overlap, indicating distinct developmental pathways. As the infection resolved, Tbet+CD11c+ B cells localized to the marginal zone where splenic retention depended on integrins LFA-1 and VLA-4, forming a competitive memory subset that contributed to antibody production and secondary GC seeding upon rechallenge. Therefore, Tbet+CD11c+ B cells comprise a GC-independent memory subset capable of rapid and robust recall responses.