ROLE OF RHEUMATOID FACTOR IN IMMUNOREGULATION

在人类中，类风湿因子(RF)产生的增加是 与类风湿性关节炎(RA)和其他自身免疫相关 综合征，慢性病毒和细菌感染，以及继发性 抗原挑战。根据假设，射频对 类风湿关节炎患者淋巴细胞功能亢进与炎症特征 以及对正常人群正在进行的抗体反应的调节 研究对象。这一假设是基于射频的能力 识别自体免疫球蛋白；因此，RF可能有助于 形成生物活性免疫复合体(IC)。 到目前为止产生的初步数据表明，含有RF的 从RF患者的血浆中分离出的IC能够诱导 正常的单个核细胞培养，许多免疫学的 类风湿性关节炎滑膜特有的现象，例如 B细胞向浆细胞分化的刺激作用及其机制 刺激白细胞介素1和花生四烯酸代谢产物的释放 来自单核细胞。将开始研究RF-IC的特性 从自身免疫患者的血浆和滑液中分离出来 淋巴细胞和单核细胞活化参数的测定 通过这些准备。其他初步数据显示，FC 酶降解产生的区域片段 免疫球蛋白也能引起上述效应。 因此，将启动研究，以确定这些活跃的 RA滑液和血浆中的碎片，以进一步定位 Fc区片段中的活性多肽序列，以及 确定单核细胞是否能够将RF-IC降解为 免疫刺激Fc区片段。最后，早期研究 已经表明，不含IC的单克隆人IgM RF能够 抑制有丝分裂原诱导的正常人B细胞分化 单个核细胞培养。因此，将启动研究，以 解决这些准备工作调节B细胞的机制 细胞功能。

In humans, increases in rheumatoid factor (RF) production are associated with rheumatoid arthritis (RA) and other autoimmune syndromes, chronic viral and bacterial infections, and secondary antigen challenge. It is hypothesized that RF contributes to the lymphocyte hyperactivity and inflammation characteristic of RA and the regulation of ongoing antibody responses in normal subjects. This hypothesis is based on the ability of RF to recognize autologous IgG; thus RF could contribute to the formation of biologically-active immune complexes (IC). Preliminary data generated thus far indicate that RF-containing IC isolated from the plasma of RF patients are able to induce, in normal mononuclear cell cultures, many of the immunological phenomena characteristic of the RA synovium, e.g., the stimulation of B cell differentiation to plasma cells and the stimulation of interleukin-1 and arachidonate metabolite release from monocytes. Studies will be initiated to characterize RF-IC from plasma and synovial fluid of autoimmune patients and to determine the parameters of lymphocyte and monocyte activation by these preparations. Other preliminary data indicate that Fc region fragments resulting from the enzymatic degradation of immunoglobulin also elicit the effects described above. Therefore, studies will be initiated to identify these active fragments in RA synovial fluid and plasma, to further localize active peptide sequences in Fc region fragments, and to determine whether monocytes are able to degrade RF-IC into immunostimulatory Fc region fragments. Finally, early studies have revealed that monoclonal human IgM RF, free of IC, is able to inhibit mitogen-induced B cell differentiation in normal human mononuclear cell cultures. Therefore, studies will be initiated to address the mechanism by which these preparations regulate B cell function.