Neo-epitopes emerging in the degenerative hippocampal granules of aged mice can be recognized by natural IgM auto-antibodies
Neo-epitopes emerging in the degenerative hippocampal granules of aged mice can be recognized by natural IgM auto-antibodies
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DOI：
10.1186/s12979-015-0050-z
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发表时间：
2015-11-24
影响因子：
7.9
通讯作者：
Pelegri, Carme
中科院分区：
文献类型：
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作者：
Manich, Gemma;Auge, Elisabet;Pelegri, Carme
背景：在大多数品系的小鼠海马区，随着年龄的增长，退行性颗粒结构逐渐出现。我们最近报道，这些颗粒包含一个新的表位，该表位被IgM抗体识别为许多商业抗体中的污染物，这些抗体来自小鼠腹水和小鼠或兔血清。我们假设这些抗新表位IgM实际上是自然产生的自身抗体，它们是在胎儿阶段自发产生的，以前没有接触外部抗原，其谱系和反应模式已经通过进化确定，在物种内甚至物种之间都非常稳定。结果：在目前的工作中，我们发现来自ICR-CD1、BALB/C和SAMP8品系的小鼠在所有测试年龄的血浆中都有抗新表位IgM抗体，即使在特定的机会性无病原体条件下保持也是如此。此外，我们还发现这些抗neo表位的IgM也存在于兔、山羊和大鼠血清中。我们还发现，在每只呈现海马体颗粒的小鼠中，其血浆中包含的抗neo表位IgM识别其自身颗粒中的neo表位。结论：本研究得出的结论是，抗neo表位IgM是小鼠和其他物种血浆中广泛存在的天然自身抗体。这些天然自身抗体的存在不仅解释了为什么它们经常被发现为商业抗体中的污染物，而且还为基于天然IgM和新表位的病理性脑过程的治疗和诊断铺平了道路。
Background: Degenerative granular structures appear progressively with age in the hippocampus of most mouse strains. We recently reported that these granules contain a neo-epitope that is recognised by IgM antibodies present as contaminants in many commercial antibodies obtained from mouse ascites and mouse or rabbit serum. We hypothesise that these anti-neo-epitope IgMs are in fact natural auto-antibodies that are generated spontaneously during the foetal stage without previous contact with external antigens and whose repertoire and reactivity pattern have been determined through evolution, being remarkably stable within species and even between species.Findings: In the present work we found that mice from the ICR-CD1, BALB/C and SAMP8 strains have anti-neoepitope IgM antibodies in their plasma at all ages tested and even when maintained under specific opportunistic pathogen-free conditions. Moreover, we determined that these anti-neo-epitope IgMs are also present in rabbit, goat and rat serum. We also found that, in each mouse that presented hippocampal granules, the anti-neo-epitope IgMs contained in its plasma recognised the neo-epitopes in its own granules.Conclusions: This study led to the conclusion that anti-neo-epitope IgMs are widespread natural auto-antibodies contained in the plasma of mice and other species. The presence of these natural auto-antibodies not only explains why they are frequently found as contaminants in commercial antibodies, but also paves the way for a new approach to a treatment and diagnosis of pathological brain processes based on natural IgMs and neo-epitopes.