@article{2b3685cdd17d427b987e51725f43c8fa,
title = "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.",
keywords = "apoptosis, autoimmunity, B cells, germinal center, tingible body macrophages",
author = "Grootveld, {Abigail K.} and Wunna Kyaw and Veera Panova and Lau, {Angelica W.Y.} and Emily Ashwin and Guillaume Seuzaret and Rama Dhenni and Bhattacharyya, {Nayan Deger} and Khoo, {Weng Hua} and Mat{\'e} Biro and Tanmay Mitra and Michael Meyer-Hermann and Patrick Bertolino and Masato Tanaka and Hume, {David A.} and Croucher, {Peter I.} and Robert Brink and Akira Nguyen and Oliver Bannard and Phan, {Tri Giang}",
note = "Funding Information: This project is supported by the Australian National Health and Medical Research Council (NHMRC) Ideas Grant APPID2003662. T.G.P. and P.I.C. and this work are supported by Mrs. Janice Gibb and the Ernest Heine Family Foundation. P.I.C. (APPID2009010), R.B. (APPID2008356), and T.G.P. (APPID1155678) are supported by Investigator Grants and Fellowships from the NHMRC. A.K.G. and W.K. are supported by an Australian Government Research Training Scholarship and R.D. by a UNSW Scientia PhD Scholarship. O.B. and this study were funded by The Wellcome Trust (220219/Z/20/Z) and by the Medical Research Council (MRC) through core funding to the MRC Human Immunology Unit and MRC WIMM. This research was funded in whole, or in part, by the Wellcome Trust [220219/Z/20/Z]. Data and code availability - Single-cell RNA-seq data have been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table. Intravital imaging, confocal microscopy and FACS data reported in this paper will be shared by the lead contact upon request. - All original code has been deposited at Zenodo and is publicly available as of the date of publication. DOIs are listed in the key resources table. - Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.",
year = "2023",
month = mar,
day = "16",
doi = "10.1016/j.cell.2023.02.004",
language = "English",
volume = "186",
pages = "1144--1161.e18",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}