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一种新的体内滤泡树突状细胞依赖性免疫体介导的将抗原递呈给抗原处理细胞的机制。

A novel in vivo follicular dendritic cell-dependent iccosome-mediated mechanism for delivery of antigen to antigen-processing cells.

作者信息

Szakal A K, Kosco M H, Tew J G

机构信息

Department of Anatomy, Medical College of Virginia, Richmond 23298.

出版信息

J Immunol. 1988 Jan 15;140(2):341-53.

PMID:3257233
Abstract

Recent scanning electron microscopic studies on isolated follicular dendritic cells (FDC) showed that dendrites of certain FDC were "beaded," i.e., consisting of a series of interconnected immune complex coated bodies (termed "iccosomes," measuring 0.3 to 0.7 micron diameter). In vitro these iccosomes detach from one another with ease. The major objectives herein were to establish whether these structures can be detected in sections and whether iccosomes serve to disseminate antigen in vivo. Beginning at day 1, the time point used for isolating beaded FDC, the popliteal lymph nodes of immune C3H mice were studied with light and transmission electron microscopy for 2 wk (i.e., at days 1, 3, 5, 8, and 14) after hind footpad injection of the histochemically detectable antigen, horseradish peroxidase (HRP). Iccosomes (0.25 to 0.38 micron diameter), contoured by a peroxidase (PO)-positive coat of HRP-anti-HRP complexes, were first detected by transmission electron microscopy at day 1 adjacent to cell bodies of certain FDC. Within their limiting membrane they contained flocculent material that was PO positive. At day 3 by light microscopy, germinal centers were seen enlarged and the antigen-retaining reticulum, composed of antigen-bearing FDC, appeared diffuse. This coincided with the transmission electron microscopic visualization of a dispersed state of iccosomes among the follicular lymphocytes. At that time iccosomes were seen attached to the surface of lymphocytes via PO-positive immune complexes and were surrounded by microvillous processes of these cells. Germinal center lymphocytes and tingible body macrophages both responded to contact with iccosomes by endocytosis. Antigen-containing tingible body macrophage were most conspicuous by light microscopy at day 5, when transmission electron microscopy showed that the majority of germinal center lymphocytes contained endocytosed HRP in secondary lysosome-like granules associated with the Golgi apparatus. The number of dispersed iccosomes was markedly reduced by day 5. In controls injected with HSA, a PO-negative antigen, lymphocytes and tingible body macrophages were PO-negative. The presence of antigen in both cell types was confirmed through the use of a gold-conjugated antigen (goat IgG). Simultaneous immunoperoxidase labeling of the same tissues with anti-Ia showed the gold conjugate containing B cells to be Ia+. Antigen-positive B cells and tingible body macrophages were greatly reduced in numbers by day 14, suggesting the intracellular fragmentation of the antigen.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

近期对分离出的滤泡树突状细胞(FDC)进行的扫描电子显微镜研究表明,某些FDC的树突呈“串珠状”,即由一系列相互连接的免疫复合物包被小体(称为“iccosomes”,直径为0.3至0.7微米)组成。在体外,这些iccosomes很容易彼此分离。本文的主要目的是确定这些结构在切片中是否能够被检测到,以及iccosomes在体内是否有助于抗原的传播。从第1天开始,即用于分离串珠状FDC的时间点,在免疫的C3H小鼠后足垫注射组织化学可检测抗原辣根过氧化物酶(HRP)后,用光学显微镜和透射电子显微镜对腘窝淋巴结进行了2周的研究(即第1、3、5、8和14天)。通过透射电子显微镜在第1天首次在某些FDC的细胞体附近检测到iccosomes(直径0.25至0.38微米),其轮廓由HRP-抗-HRP复合物的过氧化物酶(PO)阳性包被勾勒。在其限制膜内,它们含有PO阳性的絮状物质。在第3天通过光学显微镜观察到生发中心增大,由携带抗原的FDC组成的保留抗原的网状结构显得弥散。这与iccosomes在滤泡淋巴细胞中呈分散状态的透射电子显微镜观察结果一致。此时可见iccosomes通过PO阳性免疫复合物附着于淋巴细胞表面,并被这些细胞的微绒毛突起所包围。生发中心淋巴细胞和可染体巨噬细胞通过内吞作用对与iccosomes接触均有反应。含抗原的可染体巨噬细胞在第5天通过光学显微镜最为明显,此时透射电子显微镜显示大多数生发中心淋巴细胞在与高尔基体相关的次级溶酶体样颗粒中含有内吞的HRP。到第5天时,分散的iccosomes数量明显减少。在注射了PO阴性抗原人血清白蛋白(HSA)的对照中,淋巴细胞和可染体巨噬细胞均为PO阴性。通过使用金标记抗原(山羊IgG)证实了两种细胞类型中均存在抗原。用抗Ia对相同组织进行同时免疫过氧化物酶标记显示,含金缀合物的B细胞为Ia阳性。到第14天时,抗原阳性B细胞和可染体巨噬细胞数量大幅减少,提示抗原在细胞内发生了碎片化。(摘要截选至400字)

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