Goodman M G
J Immunol. 1987 Jul 1;139(1):142-6.
In previous studies it has been demonstrated that a T cell-like differentiation signal is transmitted by C8-substituted guanine ribonucleosides such as 8-mercaptoguanosine (8MGuo) to antigen-stimulated B cells. A large subset of potentially reactive B cells remains unresponsive to antigen even in the presence of signals provided by these nucleosides except when this signal is preceded by a soluble activity present in mixed lymphocyte culture supernatants. Studies with purified preparations of interleukin (IL)-1, IL-2, IL-3, granulocyte-macrophage colony stimulating factor, B cell stimulatory factor 1 (IL-4), and B cell growth factor II (IL-5) indicated that none of these activities is capable of synergizing with 8MGuo to augment B cell responsiveness to antigen. Therefore, supernatants from a number of cloned cell lines were examined for activity that could synergize with 8MGuo, in order to determine the cellular source of this activity. Soluble products secreted by cloned 24/G1 T cells act synergistically with 8MGuo to evoke enhanced antibody responses to specific antigen in populations of purified B cells. Because concanavalin (Con) A-activated 24/G1 cells produce large quantities of interferon-gamma (IFN-gamma), the possibility that interferons might mediate synergy with 8MGuo was investigated. Purified murine IFN-gamma is unable to interact synergistically with 8MGuo; moreover, treatment of active 24/G1 supernatants with monoclonal anti-IFN-gamma antibodies or at pH 2 fails to abrogate their ability to synergize. In contrast to IFN-gamma, when B cells were supplemented with either IFN-alpha or IFN-beta, antigen-dependent synergy with 8MGuo was observed. However, abrogation of IFN-alpha and IFN-beta activity with specific antibodies fails to interfere with synergy between 8MGuo and mixed lymphocyte culture or Con A supernatants. Therefore, it appears that although IFN-alpha and IFN-beta are not responsible for the synergizing activity present in activated T cell supernatants, they nonetheless represent a previously unrecognized source of synergizing activity.
在先前的研究中已证明，一种T细胞样分化信号可由C8取代的鸟嘌呤核糖核苷如8-巯基鸟苷（8MGuo）传递给抗原刺激的B细胞。即使存在这些核苷提供的信号，很大一部分潜在反应性B细胞对抗原仍无反应，除非在混合淋巴细胞培养上清液中存在的一种可溶性活性先于该信号出现。对白介素（IL）-1、IL-2、IL-3、粒细胞-巨噬细胞集落刺激因子、B细胞刺激因子1（IL-4）和B细胞生长因子II（IL-5）的纯化制剂进行的研究表明，这些活性均不能与8MGuo协同作用以增强B细胞对抗原的反应性。因此，检测了许多克隆细胞系的上清液中与8MGuo协同作用的活性，以确定该活性细胞来源。克隆的24/G1 T细胞分泌的可溶性产物与8MGuo协同作用，在纯化的B细胞群体中引发对特定抗原增强的抗体反应。由于伴刀豆球蛋白（Con）A激活的24/G1细胞产生大量干扰素-γ（IFN-γ），因此研究了干扰素可能介导与8MGuo协同作用的可能性。纯化的小鼠IFN-γ不能与8MGuo协同作用；此外，用单克隆抗IFN-γ抗体或在pH 2条件下处理活性24/G1上清液并不能消除其协同作用能力。与IFN-γ相反，当B细胞补充IFN-α或IFN-β时，观察到与8MGuo的抗原依赖性协同作用。然而，用特异性抗体消除IFN-α和IFN-β活性并不能干扰8MGuo与混合淋巴细胞培养物或Con A上清液之间的协同作用。因此，似乎尽管IFN-α和IFN-β不负责活化T细胞上清液中存在的协同活性，但它们仍然代表了一种以前未被认识的协同活性来源。
