生物
生发中心
细胞生物学
程序性细胞死亡
细胞凋亡
抗原
细胞
细胞内
下调和上调
免疫学
遗传学
基因
B细胞
抗体
作者
Abigail K. Grootveld,Wunna Kyaw,Veera Panova,Angelica W.Y. Lau,Emily Ashwin,Guillaume Seuzaret,Rama Dhenni,Nayan D. Bhattacharyya,Weng Hua Khoo,Maté Biro,Tanmay Mitra,Michael Meyer‐Hermann,Patrick Bertolino,Masato Tanaka,David Hume,Peter I. Croucher,Robert Brink,Akira Nguyen,Oliver Bannard,Tri Giang Phan
出处
期刊:Cell
[Elsevier]
日期:2023-03-01
卷期号:186 (6): 1144-1161.e18
被引量:9
标识
DOI:10.1016/j.cell.2023.02.004
摘要
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.
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