Department of Systems Immunology, Weizmann Institute of Science , Rehovot, Israel.
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research , Braunschweig, Germany.
J Exp Med. 2023 Apr 3;220(4). doi: 10.1084/jem.20222173. Epub 2023 Jan 27.
Antibody affinity maturation depends on the formation of germinal centers (GCs) in lymph nodes. This process generates a massive number of apoptotic B cells, which are removed by a specialized subset of phagocytes, known as tingible body macrophages (TBMs). Although defects in these cells are associated with pathological conditions, the identity of their precursors and the dynamics of dying GC B cell disposal remained unknown. Here, we demonstrate that TBMs originate from pre-existing lymph node-resident precursors that enter the lymph node follicles in a GC-dependent manner. Intravital imaging shows that TBMs are stationary cells that selectively phagocytose GC B cells via highly dynamic protrusions and accommodate the final stages of B cell apoptosis. Cell-specific depletion and chimeric mouse models revealed that GC B cells drive TBM formation from bone marrow-derived precursors stationed within lymphoid organs prior to the immune challenge. Understanding TBM dynamics and function may explain the emergence of various antibody-mediated autoimmune conditions.
抗体亲和力成熟依赖于淋巴结生发中心（GC）的形成。这个过程会产生大量凋亡的 B 细胞，这些细胞被称为可染色体巨噬细胞（TBMs）的一类特殊吞噬细胞清除。尽管这些细胞的缺陷与病理状况有关，但它们的前体细胞的身份和死亡 GC B 细胞的清除动力学仍然未知。在这里，我们证明 TBMs 来源于预先存在的淋巴结驻留前体细胞，这些前体细胞以依赖 GC 的方式进入淋巴结滤泡。活体成像显示，TBMs 是固定的细胞，通过高度动态的突起选择性吞噬 GC B 细胞，并容纳 B 细胞凋亡的最后阶段。细胞特异性耗竭和嵌合小鼠模型表明，在免疫挑战之前，GC B 细胞从骨髓来源的前体细胞中驱动 TBM 的形成，这些前体细胞驻留在淋巴器官内。了解 TBM 的动力学和功能可能有助于解释各种抗体介导的自身免疫疾病的出现。
