Lindhout E, van Eijk M, van Pel M, Lindeman J, Dinant H J, de Groot C
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Immunol. 1999 May 15;162(10):5949-56.
The production of IgG rheumatoid factors in the inflamed synovium of many patients with rheumatoid arthritis (RA) implies that local sites exist where plasma cell precursors undergo isotype switching and affinity maturation by somatic mutation and selection. Lymphonodular infiltrates of the synovium-containing germinal centers (GCs), are candidates to fulfill such function in the rheumatoid patient. It has been suggested that these GCs are organized around, obviously ectopic, follicular dendritic cells (FDCs). The present study attempts to find out whether these putative FDCs 1) are specific for RA, 2) have the same phenotype and functional capacity as FDCs in lymphoid organs, and 3) may locally differentiate from fibroblast-like synoviocytes (FLS). Synovial biopsies from patients with RA versus non-RA, yet arthritic backgrounds, were compared. Cells with the FDC phenotype were found in both RA and non-RA tissues as well as in single cell suspensions thereof. When FLS were cultured in vitro, part of these cell lines could be induced with IL-1beta and TNF-alpha to express the FDC phenotype, irrespective of their RA or non-RA background. By contrast, the FDC function, i.e., stable binding of GC B cells and switching off the apoptotic machinery in B cells, appeared to be the prerogative of RA-derived FLS only. The present data indicate that FDC function of FLS in RA patients is intrinsic and support the idea that synovial fibroblast-like cells have undergone some differentiation process that is unique for this disease.
许多类风湿关节炎(RA)患者炎症滑膜中IgG类风湿因子的产生表明,存在局部位点,浆细胞前体在这些位点通过体细胞突变和选择进行同种型转换和亲和力成熟。含有生发中心(GCs)的滑膜淋巴小结浸润是类风湿患者中履行这种功能的候选者。有人提出,这些生发中心围绕明显异位的滤泡树突状细胞(FDCs)组织而成。本研究试图弄清楚这些假定的FDCs是否:1)对RA具有特异性;2)与淋巴器官中的FDCs具有相同的表型和功能能力;3)可能局部地从成纤维细胞样滑膜细胞(FLS)分化而来。对患有RA与非RA但有关节炎背景的患者的滑膜活检进行了比较。在RA和非RA组织及其单细胞悬液中均发现了具有FDC表型的细胞。当FLS在体外培养时,无论其RA或非RA背景如何,这些细胞系中的一部分都可以用IL-1β和TNF-α诱导表达FDC表型。相比之下,FDC功能,即GC B细胞的稳定结合和B细胞凋亡机制的关闭,似乎仅是源自RA的FLS的特权。目前的数据表明,RA患者中FLS的FDC功能是内在的,并支持滑膜成纤维细胞样细胞经历了该疾病特有的某种分化过程这一观点。