Journal article
Apoptotic cell fragments locally activate tingible body macrophages in the germinal center
- Abstract:
- Germinal centers (GCs) that form within lymphoid follicles during antibody responses are sites of massive cell death. Tingible body macrophages (TBMs) are tasked with apoptotic cell clearance to prevent secondary necrosis and autoimmune activation by intracellular self antigens. We show by multiple redundant and complementary methods that TBMs derive from a lymph node-resident, CD169-lineage, CSF1R-blockade-resistant precursor that is prepositioned in the follicle. Non-migratory TBMs use cytoplasmic processes to chase and capture migrating dead cell fragments using a “lazy” search strategy. Follicular macrophages activated by the presence of nearby apoptotic cells can mature into TBMs in the absence of GCs. Single-cell transcriptomics identified a TBM cell cluster in immunized lymph nodes which upregulated genes involved in apoptotic cell clearance. Thus, apoptotic B cells in early GCs trigger activation and maturation of follicular macrophages into classical TBMs to clear apoptotic debris and prevent antibody-mediated autoimmune diseases.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 13.2MB, Terms of use)
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- Publisher copy:
- 10.1016/j.cell.2023.02.004
Authors
- Publisher:
- Cell Press
- Journal:
- Cell More from this journal
- Volume:
- 186
- Issue:
- 6
- Pages:
- 1144-1161.E18
- Publication date:
- 2023-03-02
- Acceptance date:
- 2023-01-31
- DOI:
- EISSN:
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1097-4172
- ISSN:
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0092-8674
- Language:
-
English
- Keywords:
- Pubs id:
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1331105
- Local pid:
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pubs:1331105
- Deposit date:
-
2023-03-03
- ARK identifier:
Terms of use
- Copyright holder:
- Grootveld et al.
- Copyright date:
- 2023
- Rights statement:
- Copyright 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Notes:
- This research was funded in whole, or in part, by the Wellcome Trust [220219/Z/20/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission.
- Licence:
- CC Attribution (CC BY)
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