Kaplan S, Hyman K, Brooks R, Wakai M, Hashimoto S, Furie R, Chiorazzi N
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.
Clin Immunol Immunopathol. 1993 Jan;66(1):18-25. doi: 10.1006/clin.1993.1003.
In an effort to study disease-related autoantibodies in rheumatoid arthritis (RA), rheumatoid factor (RF)-producing B cell lines were developed from the heterogeneous B cell populations infiltrating the synovial tissue of patients with arthritis. Over 125 EBV-transformed B cell cultures were derived from three patients: one with early pre-erosive RA, one with advanced RA, and one with osteoarthritis (OA). IgM, IgG, and IgA RF-producing B cell lines were found in all three series but with several significant differences. In each of the two RA patients, 22% of the Ig-producing cell lines secreted RF compared to 7% in the OA patient. The isotypes of these RF were mostly IgM in the early RA (62%) and the OA patient (60%) as contrasted to predominantly IgA (75%) and, to a lesser extent, IgG (12.5%) in the advanced RA patient. Analyses of the light (L) chain composition of these RF revealed that 82% of the IgM RF used kappa L chains whereas only 31% of the non-IgM RF used kappa chains. Antigen-binding analyses of these RF revealed that all the synovial tissue-derived RF from the advanced RA patient exhibited antigen binding specificities restricted to a narrow range of gamma globulins. In contrast, the synovial RF of the other two patients were either reactive with a broader spectrum of gamma globulins or reactive with a variety of unrelated antigens. In every instance, the gamma globulin-specific RF were of all three major isotypes whereas the polyreactive RF were restricted to the IgM isotype. These data demonstrate that synovial B cells from both RA and OA patients can produce RF and that significant differences can exist among patients in the percentage of RF generated and their H and L chain isotype distribution. The reversal of the kappa:lambda ratio among the IgG and IgA RF and the more restricted antigen-binding specificities of the IgG and IgA vs IgM RF suggest that a non-stochastic, possibly antigen-driven selection process was involved in their generation. The relevance of these differences in RF precursor frequency, H and L chain distribution, and antigen specificity to these two diseases warrants further investigation.
为了研究类风湿关节炎（RA）中与疾病相关的自身抗体，从浸润关节炎患者滑膜组织的异质性B细胞群体中建立了产生类风湿因子（RF）的B细胞系。超过125个EB病毒转化的B细胞培养物来自三名患者：一名患有早期侵蚀前RA，一名患有晚期RA，一名患有骨关节炎（OA）。在所有三个系列中均发现了产生IgM、IgG和IgA RF的B细胞系，但存在一些显著差异。在两名RA患者中，22%的产生Ig的细胞系分泌RF，而OA患者中这一比例为7%。这些RF的同种型在早期RA患者（62%）和OA患者（60%）中大多为IgM，而在晚期RA患者中主要为IgA（75%），在较小程度上为IgG（12.5%）。对这些RF的轻链（L）组成分析显示，82%的IgM RF使用κ轻链，而只有31%的非IgM RF使用κ链。对这些RF的抗原结合分析显示，来自晚期RA患者的所有滑膜组织来源的RF表现出局限于窄范围γ球蛋白的抗原结合特异性。相比之下，其他两名患者的滑膜RF要么与更广泛的γ球蛋白反应，要么与多种无关抗原反应。在每种情况下，γ球蛋白特异性RF属于所有三种主要同种型，而多反应性RF仅限于IgM同种型。这些数据表明，RA和OA患者的滑膜B细胞均可产生RF，并且患者之间产生RF的百分比及其重链和轻链同种型分布可能存在显著差异。IgG和IgA RF中κ:λ比例的逆转以及IgG和IgA RF与IgM RF相比更受限的抗原结合特异性表明，在其产生过程中涉及非随机的、可能由抗原驱动的选择过程。这些RF前体频率、重链和轻链分布以及抗原特异性的差异与这两种疾病的相关性值得进一步研究。
