Goodman M G, Weigle W O
J Immunol. 1984 Dec;133(6):2910-4.
The mechanism by which increased numbers of antigen-responsive B cells are generated in the presence of antigen and the C8-substituted guanine ribonucleoside, 8-mercaptoguanosine (8MGuo), has been investigated. Augmentation of the primary humoral response of splenocytes to antigen cannot be ascribed to the additive effects of the underlying antigen-specific response and the nonspecific (polyclonal) response induced by 8MGuo. This is clear from a consideration of the magnitude of the responses involved, as well as from a murine model (the SJL mouse) that does not generate a nonspecific response to the substituted nucleoside but responds to it with the usual degree of immunoenhancement in the presence of antigen. Other approaches suggest that two mechanisms are involved in adjuvanticity, one whereby preexisting antigen-specific B cells undergo clonal expansion, and one in which cells not normally participating in the response are recruited in the absence of clonal expansion. The latter mechanism appears to be the dominant one insofar as models in which 8MGuo-induced proliferation fails to occur (such as after irradiation, or in the SJL mouse) nonetheless exhibit strong adjuvant effects. Analysis of precursor frequency of antigen-specific B cells indicates that for each mature, antigen-responsive B cell present in adult murine spleen, an average of four additional cells can be recruited by the conjoint actions of antigen and 8MGuo. One group subject to such recruitment is the immature antigen-specific B cell, whose degree of functional maturity is accelerated in the presence of antigen and 8MGuo.
我们已经研究了在存在抗原和C8取代的鸟嘌呤核糖核苷8-巯基鸟苷（8MGuo）的情况下，如何产生更多数量的抗原反应性B细胞的机制。脾细胞对抗原的初次体液反应增强，不能归因于潜在的抗原特异性反应和8MGuo诱导的非特异性（多克隆）反应的累加效应。从所涉及反应的程度，以及从对取代核苷不产生非特异性反应，但在存在抗原时以通常程度的免疫增强做出反应的小鼠模型（SJL小鼠）中，可以清楚地看出这一点。其他方法表明，佐剂性涉及两种机制，一种是预先存在的抗原特异性B细胞进行克隆扩增，另一种是在没有克隆扩增的情况下招募通常不参与反应的细胞。就8MGuo诱导的增殖未能发生的模型（如照射后或SJL小鼠）而言，后一种机制似乎是主要机制，尽管如此，这些模型仍表现出强烈的佐剂作用。对抗原特异性B细胞前体频率的分析表明，对于成年小鼠脾脏中存在的每个成熟的、抗原反应性B细胞，抗原和8MGuo的联合作用平均可以再招募四个细胞。受这种招募的一组细胞是未成熟的抗原特异性B细胞，其功能成熟程度在存在抗原和8MGuo的情况下会加速。
