Sherr D H, Braun J, Dorf M E
J Immunol. 1987 Apr 1;138(7):2057-62.
Previous work has shown that the expression of a predominant family of idiotypic determinants (NPb) in the in vitro response to the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten is dependent on helper activity provided by Ly-1- and Ig-bearing B cells called BH. The ability of these BH cells to perform this idiotype-specific, genetically controlled helper function is related to the NPb idiotype specificity of their cell surface receptors. However, the means by which BH cells communicate with and stimulate NPb idiotypic B cell subsets is unknown. In this paper, an Ly-1- and immunoglobulin-bearing B helper cell hybridoma is described. Supernatants from the hybridoma or its subclones were shown to specifically help the response of NPb idiotypic PFC to NP-Ficoll when added to responder cell cultures depleted of Thy-1 and Ly-1 regulatory cell populations. Under these experimental conditions hybridoma supernatants functioned in much the same fashion as populations of Ly-1- and Ig-bearing BH helper populations described previously. NPb idiotype-specific helper activity was mediated by two separable activities elaborated by the hybridoma, an anti-NPb idiotype antibody and a non-Ig (lymphokine) activity. It was shown that both the Ig and the lymphokine components were required for helper activity. Kinetics experiments showed that the anti-idiotype antibody must be added early in the response to NP-Ficoll, whereas the lymphokine fraction could be added at least as late as day 3 of a 4-day culture in order to observe NPb idiotype-specific help. The data suggest that Ly-1 B cell hybridomas may affect the responsiveness of B cell subsets initially by interaction of anti-idiotype antibody with NPb idiotypic B cell surface receptors, followed by growth or maturation signals mediated by non-Ig lymphokine(s). The possibility that the helper activity of these Ly-1 B cell hybridomas represents the combined effects of an idiotype-specific network system and nonspecific growth or maturation factor activity in direct B cell-B cell interactions is discussed.
先前的研究表明，在体外对4-羟基-3-硝基苯乙酰（NP）半抗原的反应中，一个主要的独特型决定簇家族（NPb）的表达依赖于一类被称为BH的、带有Ly-1和免疫球蛋白的B细胞所提供的辅助活性。这些BH细胞执行这种独特型特异性、基因控制的辅助功能的能力，与其细胞表面受体的NPb独特型特异性相关。然而，BH细胞与NPb独特型B细胞亚群进行沟通并刺激它们的方式尚不清楚。本文描述了一种带有Ly-1和免疫球蛋白的B辅助细胞杂交瘤。当将杂交瘤或其亚克隆的上清液添加到去除了Thy-1和Ly-1调节细胞群体的反应细胞培养物中时，显示出这些上清液能特异性地辅助NPb独特型的针对NP-菲可的浆细胞前体（PFC）的反应。在这些实验条件下，杂交瘤上清液的作用方式与先前描述的带有Ly-1和免疫球蛋白的BH辅助细胞群体非常相似。NPb独特型特异性辅助活性由杂交瘤产生的两种可分离的活性介导，一种是抗NPb独特型抗体，另一种是非免疫球蛋白（淋巴因子）活性。结果表明，免疫球蛋白和淋巴因子成分对于辅助活性都是必需的。动力学实验表明，抗独特型抗体必须在对NP-菲可的反应早期添加，而淋巴因子部分至少可以在4天培养的第3天添加，以便观察到NPb独特型特异性辅助作用。数据表明，Ly-1 B细胞杂交瘤可能最初通过抗独特型抗体与NPb独特型B细胞表面受体的相互作用，然后由非免疫球蛋白淋巴因子介导生长或成熟信号，来影响B细胞亚群的反应性。本文还讨论了这些Ly-1 B细胞杂交瘤的辅助活性代表独特型特异性网络系统和直接B细胞 - B细胞相互作用中非特异性生长或成熟因子活性的联合作用的可能性。
