Antibody affinity maturation depends on the formation of germinal centers (GCs) in lymph nodes. This process generates a massive number of apoptotic B cells, which are removed by a specialized subset of phagocytes, known as tingible body macrophages (TBMs). Although defects in these cells are associated with pathological conditions, the identity of their precursors and the dynamics of dying GC B cell disposal remained unknown. Here, we demonstrate that TBMs originate from pre-existing lymph node–resident precursors that enter the lymph node follicles in a GC-dependent manner. Intravital imaging shows that TBMs are stationary cells that selectively phagocytose GC B cells via highly dynamic protrusions and accommodate the final stages of B cell apoptosis. Cell-specific depletion and chimeric mouse models revealed that GC B cells drive TBM formation from bone marrow–derived precursors stationed within lymphoid organs prior to the immune challenge. Understanding TBM dynamics and function may explain the emergence of various antibody-mediated autoimmune conditions.
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January 27 2023
Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites
Neta Gurwicz
,
Neta Gurwicz
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
Department of Systems Immunology, Weizmann Institute of Science
, Rehovot, Israel
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Liat Stoler-Barak
,
Liat Stoler-Barak
(Supervision)
1
Department of Systems Immunology, Weizmann Institute of Science
, Rehovot, Israel
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Niklas Schwan
,
Niklas Schwan
(Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Visualization, Writing - original draft)
2
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research
, Braunschweig, Germany
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Arnab Bandyopadhyay
,
Arnab Bandyopadhyay
(Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft)
2
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research
, Braunschweig, Germany
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Michael Meyer-Hermann
,
Michael Meyer-Hermann
(Conceptualization, Formal analysis, Investigation, Methodology, Software, Supervision, Writing - original draft, Writing - review & editing)
2
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research
, Braunschweig, Germany
3
Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig
, Braunschweig, Germany
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Ziv Shulman
(Conceptualization, Data curation, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing)
1
Department of Systems Immunology, Weizmann Institute of Science
, Rehovot, Israel
Correspondence to Ziv Shulman: ziv.shulman@weizmann.ac.il
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Neta Gurwicz
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Systems Immunology, Weizmann Institute of Science
, Rehovot, Israel
Liat Stoler-Barak
Supervision
1
Department of Systems Immunology, Weizmann Institute of Science
, Rehovot, Israel
Niklas Schwan
Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Visualization, Writing - original draft
2
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research
, Braunschweig, Germany
Arnab Bandyopadhyay
Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft
2
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research
, Braunschweig, Germany
Michael Meyer-Hermann
Conceptualization, Formal analysis, Investigation, Methodology, Software, Supervision, Writing - original draft, Writing - review & editing
2
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research
, Braunschweig, Germany
3
Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig
, Braunschweig, Germany
Correspondence to Ziv Shulman: ziv.shulman@weizmann.ac.il
Disclosures: The authors declare no competing interests exist.
Received:
December 20 2022
Revision Received:
January 10 2023
Accepted:
January 11 2023
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funding
Funder(s):
European Research Council
- Award Id(s): 101001613
Funder(s):
Israel Science Foundation
- Award Id(s): 1090/18
Funder(s):
Morris Kahn Institute for Human Immunology
Funder(s):
European Molecular Biology Organization
Funder(s):
Azrieli Foundation
Funder(s):
Moross Integrated Cancer Center
Funder(s):
Miel de Botton
Funder(s):
Innovative Medicines Initiative
- Award Id(s): 101007799
Funder(s):
European Union’s Horizon 2020 research and innovation program
Funder(s):
European Federation of Pharmaceutical Industries and Associations
© 2023 Gurwicz et al.
2023
Gurwicz et al.
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 (2023) 220 (4): e20222173.
Article history
Received:
December 20 2022
Revision Received:
January 10 2023
Accepted:
January 11 2023
Connected Content
Citation
Neta Gurwicz, Liat Stoler-Barak, Niklas Schwan, Arnab Bandyopadhyay, Michael Meyer-Hermann, Ziv Shulman; Tingible body macrophages arise from lymph node–resident precursors and uptake B cells by dendrites. J Exp Med 3 April 2023; 220 (4): e20222173. doi: https://doi.org/10.1084/jem.20222173
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