中文摘要：

調控脾臟中生發中心（GC）B細胞反應的機制尚未被闡明。在本研究中，我們結合藥理學（Liposoma巨噬細胞清除劑）和遺傳學方法清除SIGN-R1?邊緣區（MZ）巨噬細胞，揭示了它們在脾臟體液免疫調控中的特定貢獻。我們發現，雖然SIGN-R1?巨噬細胞對于B細胞的初始活化并非必需，但它們對于免疫應答的成熟和生發中心B細胞的發育是必需的。當在巨噬細胞清除之前誘導濾泡輔助T（Tfh）細胞，或當Tfh反應增強時，這些缺陷可以得到糾正。此外，我們表明，在缺乏SIGN-R1?巨噬細胞的情況下，DCIR2?樹突狀細胞（DCs）——其在啟動Tfh反應中發揮關鍵作用——無法聚集到脾臟的濾泡間區，而是被移位至邊緣區。將SIGN-R1?巨噬細胞重新恢復到脾臟中，可以糾正DCIR2?DCs的定位異常，并挽救生發中心B細胞反應。我們的研究揭示了SIGN-R1?巨噬細胞在調控生發中心反應中此前未被認識到的作用，并強調了邊緣區中巨噬細胞亞群的功能特化。

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.

論文信息：

論文題目：Marginal zone SIGN-R1+ macrophages are essential for the maturation of germinal center B cells in the spleen

期刊名稱：PNAS

時間期卷：117 (22) 12295-12305

DOI: 10.1073/pnas.1921673117

產品信息：

貨號：CP-010-010

規格：10ml+10ml

品牌：Liposoma

產地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質體清除脾臟邊緣區巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于PNAS：脾臟邊緣區SIGN-R1?巨噬細胞對于生發中心B細胞的成熟具有重要作用。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法：

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.

巨噬細胞清除材料和方法文獻截圖：