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.

抗体反应期间在淋巴滤泡内形成的生发中心 (GC) 是大量细胞死亡的部位。易染体巨噬细胞 (TBM) 的任务是清除凋亡细胞，以防止细胞内自身抗原引起的继发性坏死和自身免疫激活。我们通过多种冗余和互补方法表明，TBM 源自位于卵泡中的淋巴结驻留、CD169 谱系、CSF1R 阻断抗性前体。非迁移 TBM 使用细胞质过程来使用“惰性”搜索策略追逐和捕获迁移的死细胞碎片。被附近凋亡细胞激活的滤泡巨噬细胞可以在没有 GC 的情况下成熟为 TBM。单细胞转录组学在免疫淋巴结中鉴定出一个 TBM 细胞簇，该细胞簇上调了参与凋亡细胞清除的基因。因此，早期 GCs 中的凋亡 B 细胞触发滤泡巨噬细胞的激活和成熟成为经典的 TBM，以清除凋亡碎片并预防抗体介导的自身免疫性疾病。