Genetic timestamping of plasma cells in vivo reveals tissue-specific homeostatic population turnover

Abstract
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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 (Jchain^creERT2) 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 Jchain^creERT2 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.

The following previously published data sets were used

(2008) ImmGen ULI RNA-seq data
NCBI Gene Expression Omnibus, GSE127267.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE127267

Article and author information

Author details

An Qi Xu

Immunity and Cancer, The Francis Crick Institute, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8008-6462
Rita R Barbosa

Immunity and Cancer, The Francis Crick Institute, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Dinis Pedro Calado

Immunity and Cancer, The Francis Crick Institute, London, United Kingdom

For correspondence
dinis.calado@crick.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8239-7184

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

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.