Vijay Godhev Kumar Manakkat, Zhou Ming, Thakkar Kairavee, Rothrauff Abigail, Chawla Amanpreet Singh, Chen Dianyu, Lau Louis Chi-Wai, Habib Peter, Chetal Kashish, Chhibbar Prabal, Fan Jingyu, Das Jishnu, Joglekar Alok, Borghesi Lisa, Salomonis Nathan, Xu Heping, Singh Harinder
Center for Systems Immunology and Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
These authors contributed equally.
Res Sq. 2023 Sep 6:rs.3.rs-3296446. doi: 10.21203/rs.3.rs-3296446/v1.
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. Using a model antigen, 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 scRNA-seq+BCR-seq in spleen and bone marrow compartments, coupled with adoptive transfer experiments, reveal a novel 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 followed by reduced antigen availability.
通过生发中心（GC）反应可产生寿命各异的亲和力成熟浆细胞（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。利用一种模型抗原，我们证明了PC前体的双相生成，其中生成长寿骨髓PC的前体优先在GC反应的后期产生。在脾脏和骨髓区室中使用scRNA-seq+BCR-seq进行克隆追踪，并结合过继转移实验，揭示了一种新的PC过渡状态，该状态可产生功能上有能力的PC前体。后者经历克隆扩增，这依赖于TIGIT的诱导性表达。我们基于延长的抗原接触随后抗原可用性降低，提出了一种长寿PC前体增殖和编程的模型。
