本期文章：《细胞》：Online/在线发表

澳大利亚加文医学研究所Tri Giang Phan等研究人员合作发现，凋亡细胞的碎片局部激活生发中心的可染体巨噬细胞。这一研究成果于2023年3月2日在线发表在国际学术期刊《细胞》上。

研究人员表示，在抗体反应期间在淋巴滤泡内形成的生发中心（GC）是大量细胞死亡的场所。可染体巨噬细胞（Tingible body macrophage，TBM）的任务是清除凋亡细胞，以防止细胞内自我抗原造成的二次坏死和自身免疫性激活。

研究人员通过多种冗余和互补的方法表明，TBM来自于淋巴结驻留、CD169谱系、CSF1R阻断剂抗性的前体，该前体被预置在滤泡中。非迁移性的TBM使用细胞质过程来追逐和捕捉迁移的死细胞碎片，使用一种“懒惰”的搜索策略。滤泡巨噬细胞因附近凋亡细胞的存在而被激活，在没有GC的情况下，可以成熟为TBM。单细胞转录组学确定了免疫淋巴结中的一个TBM细胞群，它上调了参与凋亡细胞清除的基因。因此，早期GC中的凋亡B细胞触发了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，防止抗体介导的自身免疫性疾病。

附：英文原文

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

Author: Abigail K. Grootveld, Wunna Kyaw, Veera Panova, Angelica W.Y. Lau, Emily Ashwin, Guillaume Seuzaret, Rama Dhenni, Nayan Deger Bhattacharyya, Weng Hua Khoo, Maté Biro, Tanmay Mitra, Michael Meyer-Hermann, Patrick Bertolino, Masato Tanaka, David A. Hume, Peter I. Croucher, Robert Brink, Akira Nguyen, Oliver Bannard, Tri Giang Phan

Issue&Volume: 2023-03-02

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.

DOI: 10.1016/j.cell.2023.02.004