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）和其他自身免疫性 综合征，慢性病毒和细菌感染，以及继发性 抗原激发 假设RF有助于 类风湿关节炎淋巴细胞过度活跃和炎症特征 以及正常人中正在进行的抗体应答的调节 科目 这一假设是基于RF的能力， 识别自体IgG;因此RF可能有助于 生物活性免疫复合物（IC）的形成。 迄今为止产生的初步数据表明， 从RF患者血浆中分离的IC能够诱导， 正常单核细胞培养，许多免疫学 RA滑膜的特征性现象，例如，的 刺激B细胞分化为浆细胞， 刺激白细胞介素-1和花生四烯酸代谢物释放 单核细胞。 将启动研究以表征RF-IC 从自身免疫性患者的血浆和滑液中， 测定淋巴细胞和单核细胞活化参数 通过这些准备。 其他初步数据表明， 由酶降解产生的区域片段 免疫球蛋白也引起上述作用。 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 免疫刺激性Fc区片段。 最后，早期的研究 已经揭示，不含IC的单克隆人IgM RF能够 抑制正常人中丝裂原诱导的B细胞分化 单核细胞培养物。 因此，将开展研究， 探讨这些制剂调节B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.