Aldo-Benson M
Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
J Autoimmun. 1989 Jun;2(3):269-82. doi: 10.1016/0896-8411(89)90269-2.
In murine models of systemic lupus erythematosus and in many humans with SLE, antibodies against native DNA (dsDNA) are a major contributor to the pathogenesis of the disease. Loss of self-tolerance to the DNA antigen may be associated with B-cell defects or regulatory cell dysfunction. We have developed B-cell lines with specificity for the antigen DNA, from both the autoimmune BWF1 mouse strain and from the non-autoimmune BALB/c strain, to use in the investigation of inherent B-cell defects in autoimmunity. Six BWF1 cell lines and five BALB/c cell lines which are free of Thy1.2+ cells and esterase positive cells, and have between 35 and 89% rosetting with dsDNA-SRBC targets, have been propagated in vitro for 24-36 months. The cells are non-malignant, growth-factor dependent and have no antigen or mitogen in the growth medium. Lyt-1 positive cells are found in the cell lines, but Lyt-1 negative cells are also present. They respond to the antigen DNA-HRBC when EL-4 supernatant is present in culture, and the peak of the plaque-forming cell (PFC) response is the same for both strains. When cells from both strains are cultured with varying amounts of T-cell factors, there is no difference in spontaneous antibody-forming cell (AFC) formation or in response to anti-mu stimulation between BWF1 and BALB/c strains. BALB/c spleen cells do not respond to DNA-HRBC in this culture system, but BWF1 spleen cells, as well as cell line cells from both strains, respond to this antigen. T cells from non-responding BALB/c spleen and responding BWF1 spleen are able to suppress the immune response to DNA-HRBC of cell line B cells from both strains. Propagating B-cell lines in the presence of DNA for 2 weeks stimulates BWF1 cell line cells, but suppresses the response of BALB/c cell lines to antigen.
在系统性红斑狼疮的小鼠模型以及许多系统性红斑狼疮患者中，抗天然DNA（双链DNA）抗体是该疾病发病机制的主要促成因素。对DNA抗原的自身耐受性丧失可能与B细胞缺陷或调节细胞功能障碍有关。我们从自身免疫性BWF1小鼠品系和非自身免疫性BALB/c品系中开发了对DNA抗原具有特异性的B细胞系，用于研究自身免疫中固有的B细胞缺陷。六个BWF1细胞系和五个BALB/c细胞系已在体外传代培养24 - 36个月，这些细胞系不含Thy1.2 +细胞和酯酶阳性细胞，与双链DNA - 绵羊红细胞（dsDNA - SRBC）靶标的玫瑰花结形成率在35%至89%之间。这些细胞是非恶性的，依赖生长因子，并且生长培养基中没有抗原或有丝分裂原。在这些细胞系中发现了Lyt - 1阳性细胞，但也存在Lyt - 1阴性细胞。当培养物中存在EL - 4上清液时，它们对DNA - 人红细胞（DNA - HRBC）抗原产生反应，并且两个品系的噬斑形成细胞（PFC）反应峰值相同。当用不同量的T细胞因子培养两个品系的细胞时，BWF1和BALB/c品系在自发抗体形成细胞（AFC）形成或对抗μ刺激的反应方面没有差异。在该培养系统中，BALB/c脾细胞对DNA - HRBC无反应，但BWF1脾细胞以及两个品系的细胞系细胞对该抗原产生反应。来自无反应的BALB/c脾和有反应的BWF1脾的T细胞能够抑制两个品系细胞系B细胞对DNA - HRBC的免疫反应。在DNA存在的情况下传代培养B细胞系2周会刺激BWF1细胞系细胞，但会抑制BALB/c细胞系对抗原的反应。
