Center for Systems Immunology and Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
Nat Immunol. 2024 Jun;25(6):1097-1109. doi: 10.1038/s41590-024-01831-y. Epub 2024 May 2.
Affinity-matured plasma cells (PCs) of varying lifespans are generated through a germinal center (GC) response. The developmental dynamics and genomic programs of antigen-specific PC precursors remain to be elucidated. Here, using a model antigen in mice, we demonstrate biphasic generation of PC precursors, with those generating long-lived bone marrow PCs preferentially produced in the late phase of GC response. Clonal tracing using single-cell RNA sequencing and B cell antigen receptor sequencing in spleen and bone marrow compartments, coupled with adoptive transfer experiments, reveals a new PC transition state that gives rise to functionally competent PC precursors. The latter undergo clonal expansion, dependent on inducible expression of TIGIT. We propose a model for the proliferation and programming of precursors of long-lived PCs, based on extended antigen encounters in the GC.
通过生发中心（GC）反应产生具有不同寿命的亲和力成熟的浆细胞（PC）。抗原特异性 PC 前体的发育动力学和基因组程序仍有待阐明。在这里，我们使用小鼠中的模型抗原证明了 PC 前体的双相产生，那些产生长寿骨髓 PCs 的前体优先在 GC 反应的后期产生。通过单细胞 RNA 测序和脾脏和骨髓区室中的 B 细胞抗原受体测序进行克隆追踪，再加上过继转移实验，揭示了一种新的 PC 过渡状态，可产生功能成熟的 PC 前体。后者通过诱导性表达 TIGIT 进行克隆扩增。我们提出了一个基于 GC 中延长的抗原接触的长寿命 PC 前体增殖和编程的模型。
