Shlomchik M J, Marshak-Rothstein A, Wolfowicz C B, Rothstein T L, Weigert M G
Nature. 1987;328(6133):805-11. doi: 10.1038/328805a0.
Polyclonal activation has been proposed as the reason that autoantibodies are produced during autoimmune disease. This model denies a role for specific antigen selection of B cells and predicts instead a multiclonal population of unmutated or randomly mutated autoantibodies. We have found that the genetic features and clonal composition of spontaneously derived immunoglobulin G (IgG) antiself-IgG (rheumatoid factor (RF] autoantibodies derived from the autoimmune MRL/lpr mouse strain are inconsistent with both the predictions of this model and the actual outcome of experimental polyclonal activation. Instead we have found that MRL/lpr RFs are oligoclonal or even monoclonal in origin. They harbour numerous somatic mutations which are distributed in a way that suggests immunoglobulin-receptor-dependent selection of these mutations. In this sense, the MRL/lpr RFs resemble antibodies elicited by exogenous antigens after secondary immunization. The parallels suggest that, like secondary immune responses, antigen stimulation is important in the generation of MRL/lpr RFs.
多克隆激活被认为是自身免疫性疾病期间产生自身抗体的原因。该模型否认B细胞特异性抗原选择的作用，转而预测未突变或随机突变的自身抗体的多克隆群体。我们发现，源自自身免疫性MRL/lpr小鼠品系的自发产生的免疫球蛋白G（IgG）抗自身IgG（类风湿因子（RF））自身抗体的遗传特征和克隆组成，与该模型的预测以及实验性多克隆激活的实际结果均不一致。相反，我们发现MRL/lpr RFs起源于寡克隆甚至单克隆。它们含有大量体细胞突变，这些突变的分布方式表明这些突变是免疫球蛋白受体依赖性选择的结果。从这个意义上说，MRL/lpr RFs类似于二次免疫后由外源性抗原引发的抗体。这些相似之处表明，与二次免疫反应一样，抗原刺激在MRL/lpr RFs的产生中很重要。
