Kim H J, Krenn V, Steinhauser G, Berek C
Deutsches Rheuma ForschungsZentrum, Berlin, Germany; and Institut für Pathologie, Universität Würzburg, Germany.
J Immunol. 1999 Mar 1;162(5):3053-62.
Plasma cells are found surrounding the inflammatory infiltrates of macrophages, T, and B cells in the synovial tissue of patients with rheumatoid and reactive arthritis. This characteristic arrangement suggests that in the synovial tissue CD20+ B cells differentiate into plasma cells. To examine clonal relationships, we have used micromanipulation to separately isolate CD20+ B cells and plasma cells from single infiltrates. DNA was extracted, and from both populations the VH/VL gene repertoires was determined. The data show that in the inflamed synovial tissue activated B cells are clonally expanded. During proliferation in the network of follicular dendritic cells, V gene variants are generated by the hypermutation mechanism. Surprisingly, we do not find identical rearrangements between CD20+ B cells and plasma cells. Nevertheless, the finding of clonally related plasma cells within single infiltrates suggests that these cells underwent terminal differentiation in the synovial tissue. These results indicate that B cell differentiation in the synovial tissue is a dynamic process. Whereas CD20+ B cells may turnover rapidly, plasma cells may well be long lived and thus accumulate in the synovial tissue. The analysis of individual B cells recovered from synovial tissue opens a new way to determine the specificity of those cells that take part in the local immune reaction. This will provide new insights into the pathogenesis of chronic inflammatory diseases like rheumatoid or reactive arthritis.
在类风湿性关节炎和反应性关节炎患者的滑膜组织中，浆细胞存在于巨噬细胞、T细胞和B细胞的炎性浸润周围。这种特征性排列表明，滑膜组织中的CD20+B细胞可分化为浆细胞。为了研究克隆关系，我们采用显微操作从单个浸润灶中分别分离出CD20+B细胞和浆细胞。提取DNA，并测定这两个群体的VH/VL基因库。数据显示，在发炎的滑膜组织中，活化的B细胞发生了克隆性扩增。在滤泡树突状细胞网络中增殖期间，V基因变体通过高突变机制产生。令人惊讶的是，我们未在CD20+B细胞和浆细胞之间发现相同的重排。然而，在单个浸润灶中发现克隆相关的浆细胞表明，这些细胞在滑膜组织中经历了终末分化。这些结果表明，滑膜组织中的B细胞分化是一个动态过程。虽然CD20+B细胞可能快速更新，但浆细胞可能寿命很长，因此在滑膜组织中积累。对从滑膜组织中回收的单个B细胞进行分析，为确定参与局部免疫反应的细胞的特异性开辟了一条新途径。这将为类风湿性关节炎或反应性关节炎等慢性炎症性疾病的发病机制提供新见解。
