Genetic timestamping of plasma cells in vivo reveals tissue-specific homeostatic population turnover
- The Francis Crick Institute, United Kingdom
Abstract
Plasma cells (PC)s are essential for protection from infection, and at the origin of incurable cancers. Current studies do not circumvent limitations of removing PCs from their microenvironment and confound formation and maintenance. Also, the investigation of PC population dynamics has mostly relied on nucleotide analog incorporation that does not label quiescent cells, a property of most PCs. A main impediment is the lack of tools to perform specific genetic manipulation in vivo. Here we characterize a genetic tool (JchaincreERT2) in the mouse that permits first-ever specific genetic manipulation in PCs in vivo, across immunoglobulin isotypes. Using this tool, we found that splenic and bone marrow PC numbers remained constant over-time with the decay in genetically labelled PCs being compensated by unlabeled PCs, supporting homeostatic population turnover in these tissues. The JchaincreERT2 tool paves the way for in-depth mechanistic understanding of PC biology and pathology in vivo, in their microenvironment.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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ImmGen ULI RNA-seq dataNCBI Gene Expression Omnibus, GSE127267.
Article and author information
Author details
Dinis Pedro Calado
Funding
Cancer Research UK (FC001057)
- Dinis Pedro Calado
Medical Research Council (FC001057)
- Dinis Pedro Calado
Wellcome Trust (FC001057)
- Dinis Pedro Calado
Cancer Research UK ([C355/A26819])
- Dinis Pedro Calado
Medical Research Council (MR/J008060/1)
- Dinis Pedro Calado
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were carried out in accordance with national and institutional guidelines for animal care and were approved by The Francis Crick Institute biological resources facility strategic oversight committee (incorporating the Animal Welfare and Ethical Review Body) and by the Home Office, UK licence number PCE886633. All animal care and procedures followed guidelines of the UK Home Office according to the Animals (Scientific Procedures) Act 1986 and were approved by Biological Research Facility at the Francis Crick Institute.
Copyright
© 2020, Xu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Genetic timestamping of plasma cells in vivo reveals tissue-specific homeostatic population turnover
eLife 9:e59850.
https://doi.org/10.7554/eLife.59850
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