Hobbs M V, Feldbush T L, Needleman B W, Weiler J M
J Immunol. 1982 Mar;128(3):1470-5.
Purified human C3 was found to inhibit rat in vitro secondary antibody responses. Fifty percent inhibition of antibody-forming cell development occurred with C3 concentrations of 26 micrograms/ml. This decrease was not the result of a general toxicity or a shift in the antibody response kinetics. Using cell mixing experiments, we could not detect a C3-induced suppressor lymphocyte or macrophage. C3 was active when added to culture early (day 0 or 1 or during a 24-hr antigen prepulse) or late (day 3, 5, or 7)--the early addition being more suppressive. Regardless of the addition time, there was a characteristic 48- to 72-hr lag before the inhibitory effect was manifested. C3 could inhibit antibody-forming cell development after stimulation with the thymus-independent antigens, trinitrophenyl-Brucella abortus and dinitrophenyl-Ficoll, as well as the thymus-dependent antigens, dinitrophenyl-bovine gamma-globulin and chicken gamma-globulin suggesting that C3 was not selective for B memory cell subpopulations. Further characterization of our C3 preparation indicated that the majority of the suppressive activity resided in a small m.w. protein resembling the C3a fragment of C3. Human C3a preparations generated either by trypsin cleavage or zymosan activation of C3 were also tested in our antibody response system and were able to inhibit antibody-forming cell development. These data implicate C3 cleavage products as negative regulators of antibody formation.
纯化的人C3被发现可抑制大鼠体外二次抗体反应。当C3浓度为26微克/毫升时，抗体形成细胞的发育受到50%的抑制。这种减少并非一般毒性或抗体反应动力学改变的结果。通过细胞混合实验，我们未检测到C3诱导的抑制性淋巴细胞或巨噬细胞。C3在培养早期（第0天、第1天或在24小时抗原预脉冲期间）或晚期（第3天、第5天或第7天）添加时均具有活性——早期添加的抑制作用更强。无论添加时间如何，在抑制作用显现之前都有48至72小时的特征性延迟。C3可抑制用非胸腺依赖性抗原三硝基苯基-流产布鲁氏菌和二硝基苯基-聚蔗糖，以及胸腺依赖性抗原二硝基苯基-牛γ球蛋白和鸡γ球蛋白刺激后的抗体形成细胞发育，这表明C3对B记忆细胞亚群没有选择性。对我们的C3制剂的进一步表征表明，大部分抑制活性存在于一种分子量较小的蛋白质中，该蛋白质类似于C3的C3a片段。通过胰蛋白酶裂解或酵母聚糖激活C3产生的人C3a制剂也在我们的抗体反应系统中进行了测试，并且能够抑制抗体形成细胞的发育。这些数据表明C3裂解产物是抗体形成的负调节因子。
