Sukumar Selvakumar, El Shikh Mohey Eldin, Tew John G, Szakal Andras K
Department of Microbiology and Immunology, Virginia Commonwealth University, P.O. Box 980678, Richmond, VA 23298-0678, USA.
Cell Tissue Res. 2008 Apr;332(1):89-99. doi: 10.1007/s00441-007-0566-4. Epub 2008 Jan 31.
Follicular dendritic cells (FDCs) are immune accessory cells found in the follicles of secondary lymphoid organs where they promote B cell maturation in germinal centers (GCs) that develop following antigen exposure. Recently, we published a method for isolating functional murine FDCs in high purity. We reasoned that disruption of FDC reticula in vivo would alter FDC morphology. The present study was undertaken to determine the morphological features of isolated FDCs. FDC-M1 and immune complex (IC) labeling were used to identify FDCs in isolated preparations. Results at the light-microscopic level revealed that isolated FDCs trapped ICs, expressed FDC-M1 and cadherins, but generally appeared non-dendritic. However, at the ultrastructural level, the majority of FDCs exhibited dendrites and typical euchromatic nuclei that appeared as single, bilobed, or double nuclei. Based on morphology, four varieties of FDCs were distinguishable, possibly indicative of differences in maturity. Remarkably, ICs trapped by FDCs showed a distinctive periodic arrangement consistent with that known to induce immune responses by thymus independent-2 (TI-2) antigens that engage and cross-link multiple B cell receptors. The ability of FDCs to trap ICs and then display these T-cell-dependent antigens with repeating periodicity suggests that multiple B cell receptors are cross-linked by antigen on FDCs, thus promoting B cell stimulation and proliferation. Rapid proliferation is characteristic of the GC reaction, and the arrangement of T-dependent antigens in this periodic fashion may help to explain the profuse B cell proliferation in the GC microenvironment.
滤泡树突状细胞(FDCs)是在次级淋巴器官的滤泡中发现的免疫辅助细胞,在这些器官中,它们促进生发中心(GCs)中B细胞的成熟,生发中心在抗原暴露后形成。最近,我们发表了一种高纯度分离功能性小鼠FDCs的方法。我们推断,体内FDC网络的破坏会改变FDC的形态。本研究旨在确定分离出的FDCs的形态特征。FDC-M1和免疫复合物(IC)标记用于鉴定分离制剂中的FDCs。光学显微镜水平的结果显示,分离出的FDCs捕获ICs,表达FDC-M1和钙黏着蛋白,但通常看起来无树突状。然而,在超微结构水平上,大多数FDCs表现出树突和典型的常染色质核,这些核呈现为单核、双叶核或双核。基于形态学,可区分出四种FDCs变体,这可能表明成熟度存在差异。值得注意的是,FDCs捕获的ICs呈现出独特的周期性排列,这与已知通过胸腺非依赖性-2(TI-2)抗原诱导免疫反应的排列一致,TI-2抗原可结合并交联多个B细胞受体。FDCs捕获ICs然后以重复的周期性展示这些T细胞依赖性抗原的能力表明,多个B细胞受体在FDCs上被抗原交联,从而促进B细胞的刺激和增殖。快速增殖是GC反应的特征,T细胞依赖性抗原以这种周期性方式排列可能有助于解释GC微环境中大量的B细胞增殖。