中文摘要：
调控脾脏中生发中心（GC）B细胞反应的机制尚未被阐明。在本研究中，我们结合药理学（Liposoma巨噬细胞清除剂）和遗传学方法清除SIGN-R1⁺边缘区（MZ）巨噬细胞，揭示了它们在脾脏体液免疫调控中的特定贡献。我们发现，虽然SIGN-R1⁺巨噬细胞对于B细胞的初始活化并非必需，但它们对于免疫应答的成熟和生发中心B细胞的发育是必需的。当在巨噬细胞清除之前诱导滤泡辅助T（Tfh）细胞，或当Tfh反应增强时，这些缺陷可以得到纠正。此外，我们表明，在缺乏SIGN-R1⁺巨噬细胞的情况下，DCIR2⁺树突状细胞（DCs）——其在启动Tfh反应中发挥关键作用——无法聚集到脾脏的滤泡间区，而是被移位至边缘区。将SIGN-R1⁺巨噬细胞重新恢复到脾脏中，可以纠正DCIR2⁺DCs的定位异常，并挽救生发中心B细胞反应。我们的研究揭示了SIGN-R1⁺巨噬细胞在调控生发中心反应中此前未被认识到的作用，并强调了边缘区中巨噬细胞亚群的功能特化。
英文摘要：
The mechanisms that regulate germinal center (GC) B cell responses in the spleen are not fully understood. Here we use a combination of pharmacologic and genetic approaches to delete SIGN-R1+ marginal zone (MZ) macrophages and reveal their specific contribution to the regulation of humoral immunity in the spleen. We find that while SIGN-R1+ macrophages were not essential for initial activation of B cells, they were required for maturation of the response and development of GC B cells. These defects could be corrected when follicular helper T (Tfh) cells were induced before macrophage ablation or when Tfh responses were enhanced. Moreover, we show that in the absence of SIGN-R1+ macrophages, DCIR2+ dendritic cells (DCs), which play a key role in priming Tfh responses, were unable to cluster to the interfollicular regions of the spleen and were instead displaced to the MZ. Restoring SIGN-R1+ macrophages to the spleen corrected positioning of DCIR2+ DCs and rescued the GC B cell response. Our study reveals a previously unappreciated role for SIGN-R1+ macrophages in regulation of the GC reaction and highlights the functional specification of macrophage subsets in the MZ compartment.
论文信息：
论文题目：Marginal zone SIGN-R1+ macrophages are essential for the maturation of germinal center B cells in the spleen
期刊名称：PNAS
时间期卷：117 (22) 12295-12305
DOI: 10.1073/pnas.1921673117
产品信息：
货号：CP-010-010
规格：10ml+10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除脾脏边缘区巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于PNAS：脾脏边缘区SIGN-R1⁺巨噬细胞对于生发中心B细胞的成熟具有重要作用。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
CLLs or PBS-loaded control liposomes were purchased from Liposoma BV or Encapsula NanoSciences and were administered i.v. according to the manufacturer’s instructions. To deplete macrophages in CD169-DTR or in SIGN-R1-Cre/DTR mice, DT (Merck KGaA) was infused i.v. at 30 ng/g of body weight at 6, 4, and 1 d before immunization. The administration of DT was spread out over the course of 7 d before immunization to limit the effect of acute cell death of a large number of cells. We found that this DT administration schedule did not lead to any detectable inflammatory effects at the time of immunization. An additional DT injection was given at 3 d after immunization to ensure maintenance of SIGN-R1 macrophage depletion throughout the response.
巨噬细胞清除材料和方法文献截图：
