NEGATIVE SELECTION OF MULTIREACTIVE B-CELL CLONES IN NORMAL ADULT MICE
NEGATIVE SELECTION OF MULTIREACTIVE B-CELL CLONES IN NORMAL ADULT MICE
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DOI：
10.1002/eji.1830240616
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发表时间：
1994-06-01
影响因子：
5.4
通讯作者：
COUTINHO, A
中科院分区：
文献类型：
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作者：
GRANDIEN, A;FUCS, R;COUTINHO, A
在没有故意免疫的情况下。正常小鼠产生与多种自身和外来抗原反应的天然抗体。我们现在已经通过分析B细胞在不同分化阶段产生的抗体，讨论了这种反应性的假定生理选择及其一些克隆特征。使用抗原特异性斑点酶联免疫吸附试验（ELISA）与面板的自身和外来抗原，我们发现，新形成的B细胞，无论是从成人骨髓或新生儿脾脏，含有最高频率的IgM抗体与反应对面板。静息的外周B细胞显示出较低的此类抗体的频率，其在自然活化的脾浆细胞中是最低的。来自脂多糖刺激的骨髓和脾细胞杂交瘤在正常小鼠的单克隆IgM抗体的分析表明，大多数反应性评分斑点ELISA起源于多反应性IgM克隆。在针对大量自身抗原的Western印迹中，研究的每种多反应性IgM抗体均显示出独特和特异的反应性模式。我们的结论是，多反应性B细胞克隆是非常频繁的新生儿和成人的紧急剧目，但随后从骨髓到外周阴性选择。并且从可用的库到天然浆细胞的库。因此，天然抗体的多反应性似乎不是一种积极选择的性质，而是代表了逃脱失活或缺失的独特多反应性克隆的总和。
In the absence of intentional immunizations. normal mice produce natural antibodies that react with a variety of self and foreign antigens. We have now addressed the putative physiological selection of such reactivities and some of their clonal characteristics, by analyzing antibodies produced by B cells at different stages of differentiation. Using an antigen-specific spot-enzyme-linked immunosorbent assay (ELISA) with a panel of self and foreign antigens,we found that newly formed B cells, either from adult bone marrow or from newborn spleen, contain the highest frequencies of IgM antibodies with reactivities towards the panel. Resting peripheral B cells show lower frequencies of such antibodies, that are lowest among naturally activated splenic plasma cells. Analyses of monoclonal IgM antibodies derived from lipopolysaccharide-stimulated bone marrow and spleen cell hybridomas in normal mice show that the majority of reactivities scored in spot-ELISA originate from multireactive IgM clones. In Western blots against a large number of self antigens, each multireactive IgM antibody studied shows a unique and specific pattern of reactivity. We conclude that multireactive B cell clones are very frequent in the emergent repertoires of newborns and adults, but are subsequently negatively selected from bone marrow to periphery. and from the available repertoire to that of natural plasma cells. It, thus, seems that multireactivity of natural antibodies is not a positively selected property, but represents the sum of unique multireactive clones that have escaped inactivation or deletion.