Volkman D J, Lane H C, Fauci A S
Proc Natl Acad Sci U S A. 1981 Apr;78(4):2528-31. doi: 10.1073/pnas.78.4.2528.
The precise events associated with B cell activation in humans are a subject of intense investigation. It has been difficult to develop an in vitro model of antigen-specific triggering of antibody synthesis by human peripheral blood mononuclear cells that is independent of exogenous mitogens. In the present study a sensitive and reproducible culture system and enzyme-linked immunosorbent assay have been established wherein antigen alone is used to trigger antigen-specific antibody synthesis by mononuclear cells from subjects immunized to keyhole limpet hemocyanin (KLH). The in vitro antigen-induced anti-KLH response is comparable in magnitude to that induced by pokeweed mitogen, is predominantly IgM in isotype, and is accompanied by a simultaneous increase in polyclonal antibody production. Anti-KLH responses were seen at in vitro KLH concentrations as low as 0.05 microgram/ml. However, concentrations of KLH greater than 5 microgram/ml resulted in profound suppression of the anti-LHL response while continuing to trigger large amounts of total polyclonal immunoglobulin synthesis. This suppression by high concentrations of antigen was also observed in pokeweed mitogen-driven anti-KLH production. These observations are consistent with previous results from the mouse model showing a close association between antigen-specific and polyclonal responses and the phenomenon of antigen-induced, antigen-specific suppression. Thus, an in vitro model of antigen induction of antigen-specific antibody synthesis in human peripheral blood mononuclear cells has been demontrated and should prove useful in exploring the mechanism of human B cell activation and immunoregulation.
与人类B细胞活化相关的确切事件是深入研究的主题。开发一种独立于外源性有丝分裂原的、由人外周血单核细胞进行抗原特异性触发抗体合成的体外模型一直很困难。在本研究中，建立了一种灵敏且可重复的培养系统和酶联免疫吸附测定法，其中仅使用抗原触发来自已免疫于钥孔戚血蓝蛋白（KLH）的受试者的单核细胞进行抗原特异性抗体合成。体外抗原诱导的抗KLH反应在强度上与商陆有丝分裂原诱导的反应相当，在同种型上主要为IgM，并且伴随着多克隆抗体产生的同时增加。在低至0.05微克/毫升的体外KLH浓度下即可观察到抗KLH反应。然而，KLH浓度大于5微克/毫升会导致抗LHL反应受到显著抑制，同时继续触发大量的总多克隆免疫球蛋白合成。在商陆有丝分裂原驱动的抗KLH产生中也观察到高浓度抗原的这种抑制作用。这些观察结果与小鼠模型先前的结果一致，显示出抗原特异性和多克隆反应之间的密切关联以及抗原诱导的抗原特异性抑制现象。因此，已证明了一种在人外周血单核细胞中进行抗原特异性抗体合成的抗原诱导体外模型，并且该模型在探索人类B细胞活化和免疫调节机制方面应会证明是有用的。
