Tissue-resident B cells orchestrate macrophage polarisation and function

Ondrej Suchanek; John R. Ferdinand; Zewen K. Tuong; Sathi Wijeyesinghe; Anita Chandra; Ann Katrin Clauder; Larissa N. Almeida; Simon Clare; Katherine Harcourt; Christopher J. Ward; Rachael Bashford-Rogers; Trevor Lawley; Rudolf A. Manz; Klaus Okkenhaug; David Masopust; Menna R. Clatworthy

doi:10.1038/s41467-023-42625-4

Tissue-resident B cells orchestrate macrophage polarisation and function

Ondrej Suchanek, John R. Ferdinand, Zewen K. Tuong, Sathi Wijeyesinghe, Anita Chandra, Ann Katrin Clauder, Larissa N. Almeida, Simon Clare, Katherine Harcourt, Christopher J. Ward, Rachael Bashford-Rogers, Trevor Lawley, Rudolf A. Manz, Klaus Okkenhaug, David Masopust, Menna R. Clatworthy^*

^*Corresponding author for this work

36 Citations (Scopus)

Abstract

B cells play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells in blood and secondary lymphoid organs but whether B cells reside in non-lymphoid organs (NLO) in homeostasis is unknown. Here we identify, using intravenous labeling and parabiosis, a bona-fide tissue-resident B cell population in lung, liver, kidney and urinary bladder, a substantial proportion of which are B-1a cells. Tissue-resident B cells are present in neonatal tissues and also in germ-free mice NLOs, albeit in lower numbers than in specific pathogen-free mice and following co-housing with ‘pet-store’ mice. They spatially co-localise with macrophages and regulate their polarization and function, promoting an anti-inflammatory phenotype, in-part via interleukin-10 production, with effects on bacterial clearance during urinary tract infection. Thus, our data reveal a critical role for tissue-resident B cells in determining the homeostatic ‘inflammatory set-point’ of myeloid cells, with important consequences for tissue immunity.

Original language	English
Article number	7081
Journal	Nature Communications
Volume	14
Issue number	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-023-42625-4
Publication status	Published - 12.2023

Funding

The Clatworthy Lab is based in the University of Cambridge Molecular Immunity Unit in the MRC Laboratory of Molecular Biology and is grateful for the use of the core facilities. O.S. was supported by the Wellcome PhD\u00A0Clinical Training Fellowship 205250/Z/16/Z and National Institute of Health Research (NIHR) clinical lectureship. S.C. and K.H. were supported by Wellcome Trust Research grant 206194. J.R.F. and M.R.C. were funded by the NIHR Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit. M.R.C. was also supported by a Medical Research Council New Investigator Research Grant MR/N024907/1, Chan-Zuckerberg Initiative Human Cell Atlas Technology Development Grant, Versus Arthritis Cure Challenge Research Grant (21777) and NIHR Research Professorship RP-2017-08-ST2-002. We thank Drs Carl Anderson and Velislava Petrova (Wellcome Sanger Institute, UK) for support and useful discussions around BCR analysis. This work was performed, in part, using resources provided by the Cambridge Service for Data Driven Discovery (CSD3) operated by the University of Cambridge Research Computing Service (www.csd3.cam.ac.uk), provided by Dell EMC and Intel using Tier-2 funding from the Engineering and Physical Sciences Research Council (capital grant EP/P020259/1), and DiRAC funding from the Science and Technology Facilities Council (www.dirac.ac.uk). The Clatworthy Lab is based in the University of Cambridge Molecular Immunity Unit in the MRC Laboratory of Molecular Biology and is grateful for the use of the core facilities. O.S. was supported by the Wellcome PhD Clinical Training Fellowship 205250/Z/16/Z and National Institute of Health Research (NIHR) clinical lectureship. S.C. and K.H. were supported by Wellcome Trust Research grant 206194. J.R.F. and M.R.C. were funded by the NIHR Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit. M.R.C. was also supported by a Medical Research Council New Investigator Research Grant MR/N024907/1, Chan-Zuckerberg Initiative Human Cell Atlas Technology Development Grant, Versus Arthritis Cure Challenge Research Grant (21777) and NIHR Research Professorship RP-2017-08-ST2-002. We thank Drs Carl Anderson and Velislava Petrova (Wellcome Sanger Institute, UK) for support and useful discussions around BCR analysis. This work was performed, in part, using resources provided by the Cambridge Service for Data Driven Discovery (CSD3) operated by the University of Cambridge Research Computing Service ( www.csd3.cam.ac.uk ), provided by Dell EMC and Intel using Tier-2 funding from the Engineering and Physical Sciences Research Council (capital grant EP/P020259/1), and DiRAC funding from the Science and Technology Facilities Council ( www.dirac.ac.uk ).

Funders	Funder number
Drs Carl Anderson and Velislava Petrova
Science and Technology Facilities Council
National Institute for Health and Care Research
Wellcome Sanger Institute
NIHR Cambridge Biomedical Research Centre
University of Cambridge Molecular Immunity Unit
UK Research and Innovation
Wellcome Trust Centre for Mitochondrial Research	206194
Wellcome Trust	205250/Z/16/Z
Medical Research Council	MR/N024907/1
Engineering and Physical Sciences Research Council	EP/P020259/1
Versus Arthritis Cure Challenge Research	RP-2017-08-ST2-002, 21777

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Cite this

Suchanek, O., Ferdinand, J. R., Tuong, Z. K., Wijeyesinghe, S., Chandra, A., Clauder, A. K., Almeida, L. N., Clare, S., Harcourt, K., Ward, C. J., Bashford-Rogers, R., Lawley, T., Manz, R. A., Okkenhaug, K., Masopust, D., & Clatworthy, M. R. (2023). Tissue-resident B cells orchestrate macrophage polarisation and function. Nature Communications, 14(1), Article 7081. https://doi.org/10.1038/s41467-023-42625-4

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title = "Tissue-resident B cells orchestrate macrophage polarisation and function",

abstract = "B cells play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells in blood and secondary lymphoid organs but whether B cells reside in non-lymphoid organs (NLO) in homeostasis is unknown. Here we identify, using intravenous labeling and parabiosis, a bona-fide tissue-resident B cell population in lung, liver, kidney and urinary bladder, a substantial proportion of which are B-1a cells. Tissue-resident B cells are present in neonatal tissues and also in germ-free mice NLOs, albeit in lower numbers than in specific pathogen-free mice and following co-housing with {\textquoteleft}pet-store{\textquoteright} mice. They spatially co-localise with macrophages and regulate their polarization and function, promoting an anti-inflammatory phenotype, in-part via interleukin-10 production, with effects on bacterial clearance during urinary tract infection. Thus, our data reveal a critical role for tissue-resident B cells in determining the homeostatic {\textquoteleft}inflammatory set-point{\textquoteright} of myeloid cells, with important consequences for tissue immunity.",

author = "Ondrej Suchanek and Ferdinand, \{John R.\} and Tuong, \{Zewen K.\} and Sathi Wijeyesinghe and Anita Chandra and Clauder, \{Ann Katrin\} and Almeida, \{Larissa N.\} and Simon Clare and Katherine Harcourt and Ward, \{Christopher J.\} and Rachael Bashford-Rogers and Trevor Lawley and Manz, \{Rudolf A.\} and Klaus Okkenhaug and David Masopust and Clatworthy, \{Menna R.\}",

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doi = "10.1038/s41467-023-42625-4",

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Suchanek, O, Ferdinand, JR, Tuong, ZK, Wijeyesinghe, S, Chandra, A, Clauder, AK, Almeida, LN, Clare, S, Harcourt, K, Ward, CJ, Bashford-Rogers, R, Lawley, T, Manz, RA, Okkenhaug, K, Masopust, D & Clatworthy, MR 2023, 'Tissue-resident B cells orchestrate macrophage polarisation and function', Nature Communications, vol. 14, no. 1, 7081. https://doi.org/10.1038/s41467-023-42625-4

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AU - Suchanek, Ondrej

AU - Ferdinand, John R.

AU - Tuong, Zewen K.

AU - Wijeyesinghe, Sathi

AU - Chandra, Anita

AU - Clauder, Ann Katrin

AU - Almeida, Larissa N.

AU - Clare, Simon

AU - Harcourt, Katherine

AU - Ward, Christopher J.

AU - Bashford-Rogers, Rachael

AU - Lawley, Trevor

AU - Manz, Rudolf A.

AU - Okkenhaug, Klaus

AU - Masopust, David

AU - Clatworthy, Menna R.

PY - 2023/12

Y1 - 2023/12

N2 - B cells play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells in blood and secondary lymphoid organs but whether B cells reside in non-lymphoid organs (NLO) in homeostasis is unknown. Here we identify, using intravenous labeling and parabiosis, a bona-fide tissue-resident B cell population in lung, liver, kidney and urinary bladder, a substantial proportion of which are B-1a cells. Tissue-resident B cells are present in neonatal tissues and also in germ-free mice NLOs, albeit in lower numbers than in specific pathogen-free mice and following co-housing with ‘pet-store’ mice. They spatially co-localise with macrophages and regulate their polarization and function, promoting an anti-inflammatory phenotype, in-part via interleukin-10 production, with effects on bacterial clearance during urinary tract infection. Thus, our data reveal a critical role for tissue-resident B cells in determining the homeostatic ‘inflammatory set-point’ of myeloid cells, with important consequences for tissue immunity.

AB - B cells play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells in blood and secondary lymphoid organs but whether B cells reside in non-lymphoid organs (NLO) in homeostasis is unknown. Here we identify, using intravenous labeling and parabiosis, a bona-fide tissue-resident B cell population in lung, liver, kidney and urinary bladder, a substantial proportion of which are B-1a cells. Tissue-resident B cells are present in neonatal tissues and also in germ-free mice NLOs, albeit in lower numbers than in specific pathogen-free mice and following co-housing with ‘pet-store’ mice. They spatially co-localise with macrophages and regulate their polarization and function, promoting an anti-inflammatory phenotype, in-part via interleukin-10 production, with effects on bacterial clearance during urinary tract infection. Thus, our data reveal a critical role for tissue-resident B cells in determining the homeostatic ‘inflammatory set-point’ of myeloid cells, with important consequences for tissue immunity.

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Tissue-resident B cells orchestrate macrophage polarisation and function

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