Petersen J
Laboratory of Medical Immunology, Rigshospitalet University Hospital, Copenhagen, Denmark.
Dan Med Bull. 1988 Apr;35(2):140-57.
The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells. Synovial fluid mononuclear cells did not produce immunoglobulins in cultures stimulated with PWM, unless synovial T cells were removed and replaced with autologous blood T cells. Under these conditions synovial fluid B lymphocytes were induced by PWM to considerable IgG synthesis; fewer cells secreted IgM and IgA. About 8-9% of the induced IgM- and IgG-synthesizing cells displayed rheumatoid factor activity. Aurothiomalate markedly inhibited PWM-induced immunoglobulin production by normal lymphocytes cultured in vitro, probably by affecting monocyte/macrophage-lymphocyte interactions. The drug also had a direct inhibitory action on B lymphocytes, whereas T cells were resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究分析了类风湿关节炎（RA）患者体外B淋巴细胞的功能。讨论了金盐和青霉胺对人B淋巴细胞体外功能的影响。滑膜液单核细胞/巨噬细胞可增加多克隆诱导的和抗原诱导的血液淋巴细胞增殖，并增加由商陆有丝分裂原（PWM，一种T细胞依赖性多克隆激活剂）产生的分泌免疫球蛋白的血液B淋巴细胞数量。在大多数无细胞滑膜液标本中发现了可由单核细胞/巨噬细胞产生的淋巴刺激因子白细胞介素-1，但在少数配对血清样本中才发现。因此，体内活化的滑膜单核细胞/巨噬细胞可能调节淋巴细胞功能。与血液相比，滑膜液T淋巴细胞中T4 +（辅助/诱导）细胞较少，T8 +（抑制/细胞毒性）细胞较多。滑膜液淋巴细胞在多克隆刺激下增殖能力较差。然而，其对微生物抗原的增殖反应以及凝集素诱导的淋巴因子产生与血液淋巴细胞相当。在大约一半的RA患者中，与用血液T4 +细胞进行的类似实验相比，滑膜液中的T4 +细胞可使自体血液B淋巴细胞由PWM诱导的免疫球蛋白分泌增加到更高水平。滑膜液T8 +细胞对PWM诱导的自体单核细胞免疫球蛋白产生的抑制程度与血液T8 +细胞相同。滑膜液中很大一部分T亚群表达Ia抗原,这可能是由于体内活化所致。因此，滑膜辅助/诱导性T细胞和抑制/细胞毒性T细胞可能调节滑膜B淋巴细胞的功能活性。在从滑膜液和滑膜组织分离的单核细胞中，发现相当数量的B淋巴细胞自发分泌IgG；分泌IgM和IgA的B细胞较少。在约7%的产生IgG的细胞中检测到类风湿因子活性。滑膜液单核细胞在用PWM刺激的培养物中不产生免疫球蛋白,除非去除滑膜T细胞并用自体血液T细胞替代。在这些条件下，PWM可诱导滑膜液B淋巴细胞产生大量IgG；分泌IgM和IgA的细胞较少,约8 - 9%诱导产生IgM和IgG的细胞表现出类风湿因子活性。硫代苹果酸金钠可显著抑制体外培养的正常淋巴细胞由PWM诱导的免疫球蛋白产生，这可能是通过影响单核细胞/巨噬细胞 - 淋巴细胞相互作用实现的。该药物对B淋巴细胞也有直接抑制作用，而T细胞具有抗性。（摘要截选至400字）
