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.

不同寿命的亲和力成熟浆细胞 (PC) 是通过生发中心 (GC) 反应产生的。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，我们使用小鼠模型抗原，证明了 PC 前体的双相生成，其中那些产生长寿命骨髓 PC 的细胞优先在 GC 反应的后期产生。在脾脏和骨髓室中使用单细胞 RNA 测序和 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，该状态产生了具有功能性的 PC 前体。后者依赖于 TIGIT 的诱导表达进行克隆扩增。我们基于 GC 中延长的抗原遭遇，提出了一种长寿命 PC 前体的增殖和编程模型。