The longevity of plasma cells is dependent on their ability to access and reside in so-called niches that are predominantly located in the bone marrow. Here, by employing a traceable method to label recently generated plasma cells, we showed that homeostatic plasma cells in the bone marrow and spleen were continuously replenished by newly generated B220hiMHC-IIhi populations that progressively differentiated into B220loMHC-IIlo long-lived plasma cell (LLPC) populations. We also found that, in the bone marrow, germinal center (GC)–independent and GC-dependent plasma cells decayed similarly upon NP-CGG engagement, and both entered the B220loMHC-IIlo LLPC pool. Compared with NP+B220hiMHC-IIhi plasma cells, NP+B220loMHC-IIlo cells were more immobilized in the bone marrow niches and showed better survival potential. Thus, our results suggest that the adhesion status of bone marrow plasma cells is dynamically altered during their differentiation and is associated with provision of survival signals.
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6 February 2023
Brief Definitive Report|
December 14 2022
Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow
Takuya Koike
,
Takuya Koike
(Formal analysis, Funding acquisition, Investigation, Resources, Validation, Visualization, Writing - original draft)
1
Regulation of Host Defense Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
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Kentaro Fujii
,
Kentaro Fujii
(Conceptualization, Investigation, Methodology)
2
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
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Kohei Kometani
,
Kohei Kometani
(Methodology)
3
Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
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Noah S. Butler
,
Noah S. Butler
(Resources, Writing - review & editing)
4
Department of Microbiology and Immunology, The University of Iowa, Iowa City, IA, USA
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Kenji Funakoshi
,
Kenji Funakoshi
(Investigation)
2
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
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Shinya Yari
,
Shinya Yari
(Investigation)
5
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan
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Junichi Kikuta
,
Junichi Kikuta
(Investigation)
5
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan
6
Laboratory of Immunology and Cell Biology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
7
Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
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Masaru Ishii
,
Masaru Ishii
(Investigation, Methodology)
5
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan
6
Laboratory of Immunology and Cell Biology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
7
Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
8
Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
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Tomohiro Kurosaki
,
(Conceptualization, Funding acquisition, Supervision, Writing - original draft, Writing - review & editing)
2
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
3
Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
8
Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
Correspondence to Tomohiro Kurosaki: kurosaki@ifrec.osaka-u.ac.jp
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Wataru Ise
(Conceptualization, Funding acquisition, Supervision, Writing - original draft, Writing - review & editing)
1
Regulation of Host Defense Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
Wataru Ise: wise@ifrec.osaka-u.ac.jp
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Takuya Koike
Formal analysis, Funding acquisition, Investigation, Resources, Validation, Visualization, Writing - original draft
1
Regulation of Host Defense Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
Kentaro Fujii
Conceptualization, Investigation, Methodology
2
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
Kohei Kometani
Methodology
3
Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
Noah S. Butler
Resources, Writing - review & editing
4
Department of Microbiology and Immunology, The University of Iowa, Iowa City, IA, USA
Kenji Funakoshi
Investigation
2
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
Shinya Yari
Investigation
5
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan
Junichi Kikuta
Investigation
5
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan
6
Laboratory of Immunology and Cell Biology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
7
Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
Masaru Ishii
Investigation, Methodology
5
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan
6
Laboratory of Immunology and Cell Biology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
7
Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
8
Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
Tomohiro Kurosaki
Conceptualization, Funding acquisition, Supervision, Writing - original draft, Writing - review & editing
2
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
3
Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
8
Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan
Correspondence to Tomohiro Kurosaki: kurosaki@ifrec.osaka-u.ac.jp
Wataru Ise: wise@ifrec.osaka-u.ac.jp
Disclosures: The authors declare no competing interests exist.
Received:
October 07 2022
Revision Received:
November 07 2022
Accepted:
November 23 2022
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funding
Funder(s):
Nippon Foundation
Funder(s):
Otsuka Pharmaceutical Co., Ltd.
Funder(s):
Grand-in-Aid for JSPS Fellows
- Award Id(s): JP22J00313
Funder(s):
Grand-in-Aid for Young Scientists
- Award Id(s): JP20K16283
Funder(s):
Japan Society for the Promotion of Science KAKENHI
- Award Id(s): JP22H00450,JP18KK0227,JP20H03503
Funder(s):
SENSHIN Medical Research Foundation
Funder(s):
Uehara Memorial Foundation
Funder(s):
Naito Foundation
Funder(s):
Daiichi Sankyo Foundation of Life Science
© 2022 Koike et al.
2022
Koike et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2023) 220 (2): e20221717.
Article history
Received:
October 07 2022
Revision Received:
November 07 2022
Accepted:
November 23 2022
Citation
Takuya Koike, Kentaro Fujii, Kohei Kometani, Noah S. Butler, Kenji Funakoshi, Shinya Yari, Junichi Kikuta, Masaru Ishii, Tomohiro Kurosaki, Wataru Ise; Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow. J Exp Med 6 February 2023; 220 (2): e20221717. doi: https://doi.org/10.1084/jem.20221717
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