Ise Wataru, Koike Takuya, Shimada Nozomi, Yamamoto Hiromi, Tai Yuki, Shirai Taiichiro, Kawakami Ryoji, Kuwabara Mana, Kawai Chie, Shida Kyoko, Inoue Takeshi, Hojo Nozomi, Ichiyama Kenji, Sakaguchi Shimon, Shiroguchi Katsuyuki, Suzuki Kazuhiro, Kurosaki Tomohiro
Regulation of Host Defense Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan.
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
J Exp Med. 2025 May 5;222(5). doi: 10.1084/jem.20241019. Epub 2025 Feb 20.
Newly generated plasma cells in secondary lymphoid organs migrate to niches in the bone marrow, wherein they survive as long-lived plasma cells (LLPCs). Although LLPCs have been extensively characterized, it is still unclear what the key determinant(s) are for plasma cell longevity. One model postulates that plasma cell heterogeneity is established at the induction site, thereby instructing their longevity. Here, we found that, among newly generated IgG plasma cells, integrin β7hi marks plasma cells predisposed to home to the bone marrow, whereas integrin β7lo cells remain in secondary lymphoid organs. Mechanistically, this egress-prone fraction had a higher expression of the KLF2 transcription factor, the loss of which resulted in defective egress by downregulating S1PR1 and CD11b. Disruption of plasma cell egress results in defective antibody durability, thereby making mice more susceptible to influenza reinfection. Thus, the migration program of plasma cells established at the induction site plays a critical role in determining antibody durability.
次级淋巴器官中新生的浆细胞迁移至骨髓中的特定微环境，在那里它们作为长寿浆细胞（LLPCs）存活下来。尽管LLPCs已得到广泛研究，但浆细胞长寿的关键决定因素仍不清楚。一种模型推测，浆细胞异质性在诱导部位就已确立，从而决定了它们的寿命。在此，我们发现，在新生成的IgG浆细胞中，整合素β7高表达标记了倾向于归巢至骨髓的浆细胞，而整合素β7低表达的细胞则留在次级淋巴器官中。从机制上讲，这个易于迁出的亚群中KLF2转录因子表达较高，其缺失会通过下调S1PR1和CD11b导致迁出缺陷。浆细胞迁出的破坏会导致抗体持久性缺陷，从而使小鼠更容易再次感染流感。因此，在诱导部位确立的浆细胞迁移程序在决定抗体持久性方面起着关键作用。
