KLF2 expression in IgG plasma cells at their induction site regulates the migration program
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.
Authors
- Nozomi Hojo (ORCID: https://orcid.org/0000-0003-0641-5533)
- Katsuyuki Shiroguchi (ORCID: https://orcid.org/0000-0003-4025-8789)
- Hiromi Yamamoto
- Ryoji Kawakami (ORCID: https://orcid.org/0000-0003-2253-4559)
- Kazuhiro Suzuki (ORCID: https://orcid.org/0000-0002-9081-538X)
- Shimon Sakaguchi (ORCID: https://orcid.org/0000-0001-8265-6094)
- Wataru Ise (ORCID: https://orcid.org/0000-0003-0457-3386)
- Takeshi Inoue (ORCID: https://orcid.org/0000-0002-9972-6105)
- Kyoko Shida
- Kenji Ichiyama (ORCID: https://orcid.org/0000-0002-3340-9799)
- Tomohiro Kurosaki (ORCID: https://orcid.org/0000-0002-6352-304X)
- Chie Kawai
- Yuki Tai
- Taiichiro Shirai (ORCID: https://orcid.org/0000-0003-0231-6386)
- Takuya Koike (ORCID: https://orcid.org/0000-0002-4193-6679)
- M. Kuwabara
- N. Shimada
Institutions
- Kyoto University (JP)
- Systems Dynamics (United States) (US)
- RIKEN Center for Biosystems Dynamics Research (JP)
- Immune Regulation (United Kingdom) (GB)
- RIKEN Center for Integrative Medical Sciences (JP)
- The University of Tokyo (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2025-02-20
- DOI
- https://doi.org/10.1084/jem.20241019
- Citations
- 4
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.19
Funders
- Naito Foundation
- Takeda Science Foundation
- Uehara Memorial Foundation
- Japan Agency for Medical Research and Development
- Daiichi Sankyo Foundation of Life Science
- Otsuka Pharmaceutical
- Nippon Foundation
- SENSHIN Medical Research Foundation
- Japan Society for the Promotion of Science