Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow

Author:

Koike Takuya1ORCID,Fujii Kentaro2ORCID,Kometani Kohei3ORCID,Butler Noah S.4ORCID,Funakoshi Kenji2ORCID,Yari Shinya5ORCID,Kikuta Junichi567ORCID,Ishii Masaru5678ORCID,Kurosaki Tomohiro238ORCID,Ise Wataru1ORCID

Affiliation:

1. Regulation of Host Defense Team, Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan 1

2. Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan 2

3. Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan 3

4. Department of Microbiology and Immunology, The University of Iowa, Iowa City, IA, USA 4

5. Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan 5

6. Laboratory of Immunology and Cell Biology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan 6

7. Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan 7

8. Division of Microbiology and Immunology, Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan 8

Abstract

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.

Funder

Nippon Foundation

Otsuka Pharmaceutical Co., Ltd.

Grand-in-Aid for JSPS Fellows

Grand-in-Aid for Young Scientists

Japan Society for the Promotion of Science KAKENHI

SENSHIN Medical Research Foundation

Uehara Memorial Foundation

Naito Foundation

Daiichi Sankyo Foundation of Life Science

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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