Apoptotic cell fragments locally activate tingible body macrophages in the germinal center

• DOI: 10.1016/j.cell.2023.02.004
• Publication Date: 2023-03-02T15:41:18Z
• Authors: Abigail K. Grootveld; Wunna Kyaw; Veera Panova; Angelica W.Y. Lau; Emily Ashwin; Guillaume Seuzaret; Rama Dhenni; Nayan Deger Bhatt...; Weng Hua Khoo; Maté Biro; Tanmay Mitra; Michael Meyer-Her...; Patrick Bertolino; Masato Tanaka; David A. Hume; Peter I. Croucher; Robert Brink; Akira Nguyen; Oliver Bannard; Tri Giang Phan
• Keywords: Center (category theory)

Germinal centers (GCs) that form within lymphoid follicles during antibody responses are sites of massive cell death. Tingible body macrophages (TBMs) tasked with apoptotic clearance to prevent secondary necrosis and autoimmune activation by intracellular self antigens. We show multiple redundant complementary methods TBMs derive from a lymph node-resident, CD169-lineage, CSF1R-blockade-resistant precursor is prepositioned in the follicle. Non-migratory use cytoplasmic processes chase capture migrating dead fragments using "lazy" search strategy. Follicular activated presence nearby cells can mature into absence GCs. Single-cell transcriptomics identified TBM cluster immunized nodes which upregulated genes involved clearance. Thus, B early GCs trigger maturation follicular classical clear debris antibody-mediated diseases.