The marginal zone (MZ) of the spleen contains multiple cell types that are involved in mounting rapid immune responses against blood-borne pathogens, including conventional dendritic cells (cDCs) and MZ B cells. MZ B cells develop later than other B cell types and are sparse in neonatal mice. Here, we show that cDC2s are abundant in the MZ of neonatal compared with adult mice. We find that conditions associated with reduced MZ B cell numbers in adult mice cause increased cDC2 occupancy of the MZ. Treatment with the S1PR1-modulating drug, FTY720, causes cDC2 movement into the MZ through the indirect mechanism of displacing MZ B cells into follicles. Splenic cDC2s express high amounts of α4β1 and αLβ2 integrins and depend on these integrins and the adaptor Talin for their retention in blood-exposed regions of the spleen. Splenic CD4 T cell activation by particulate antigens is increased in mice with higher cDC2 density in the MZ, including in neonatal mice. Our work establishes requirements for homeostatic cDC2 positioning in the spleen and provides evidence that localization in blood-exposed regions around the white pulp augments cDC2 capture of particulate antigens. We suggest that MZ positioning of cDC2s partially compensates for the lack of MZ B cells during the neonatal period.
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2 November 2020
Brief Definitive Report|
August 17 2020
Requirements for cDC2 positioning in blood-exposed regions of the neonatal and adult spleen
Dan Liu
,
Dan Liu
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Howard Hughes Medical Institute, San Francisco, CA
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
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Jiaxi Wu
,
Jiaxi Wu
Investigation
1
Howard Hughes Medical Institute, San Francisco, CA
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
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Jinping An
,
Jinping An
Data curation, Investigation, Methodology, Resources
1
Howard Hughes Medical Institute, San Francisco, CA
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
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Jason G. Cyster
Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
1
Howard Hughes Medical Institute, San Francisco, CA
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
Correspondence to Jason G. Cyster: jason.cyster@ucsf.edu
Search for other works by this author on:
Dan Liu
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Howard Hughes Medical Institute, San Francisco, CA
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
Jiaxi Wu
Investigation
1
Howard Hughes Medical Institute, San Francisco, CA
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
Jinping An
Data curation, Investigation, Methodology, Resources
1
Howard Hughes Medical Institute, San Francisco, CA
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
Jason G. Cyster
Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
1
Howard Hughes Medical Institute, San Francisco, CA
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA
Correspondence to Jason G. Cyster: jason.cyster@ucsf.edu
Disclosures: J. Cyster reported consulting for several biotech companies and serving on the scientific advisory board of ALX Oncology Inc. and MiroBio Ltd. No other disclosures were reported.
Received:
December 06 2019
Revision Received:
May 06 2020
Accepted:
June 24 2020
Online Issn: 1540-9538
Print Issn: 0022-1007
© 2020 Liu et al.
2020
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 (2020) 217 (11): e20192300.
Article history
Received:
December 06 2019
Revision Received:
May 06 2020
Accepted:
June 24 2020
Citation
Dan Liu, Jiaxi Wu, Jinping An, Jason G. Cyster; Requirements for cDC2 positioning in blood-exposed regions of the neonatal and adult spleen. J Exp Med 2 November 2020; 217 (11): e20192300. doi: https://doi.org/10.1084/jem.20192300
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