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Existence of natural mouse IgG mAbs recognising epitopes shared by malondialdehyde acetaldehyde adducts and Porphyromonas gingivalis
Innate Immunity ( IF 2.8 ) Pub Date : 2021-01-14 , DOI: 10.1177/1753425920981133
Mikael Kyrklund 1, 2 , Heidi Kaski 1 , Ramin Akhi 1, 2 , Antti E Nissinen 1, 2 , Outi Kummu 1, 2 , Ulrich Bergmann 3 , Pirkko Pussinen 4 , Sohvi Hörkkö 1, 2 , Chunguang Wang 1, 2, 5
Affiliation  

Natural Abs are produced by B lymphocytes in the absence of external Ag stimulation. They recognise self, altered self and foreign Ags, comprising an important first-line defence against invading pathogens and serving as innate recognition receptors for tissue homeostasis. Natural IgG Abs have been found in newborns and uninfected individuals. Yet, their physiological role remains unclear. Previously, no natural IgG Abs to oxidation-specific epitopes have been reported. Here, we show the cloning and characterisation of mouse IgG mAbs against malondialdehyde acetaldehyde (MAA)-modified low-density lipoprotein. Sequence analysis reveals high homology with germline genes, suggesting that they are natural. Further investigation shows that the MAA-specific natural IgG Abs cross-react with the major periodontal pathogen Porphyromonas gingivalis and recognise its principle virulence factors gingipain Kgp and long fimbriae. The study provides evidence that natural IgGs may play an important role in innate immune defence and in regulation of tissue homeostasis by recognising and removing invading pathogens and/or modified self-Ags, thus being involved in the development of periodontitis and atherosclerosis.



中文翻译:

存在识别丙二醛乙醛加合物和牙龈卟啉单胞菌共有表位的天然小鼠 IgG mAb

天然抗体是由 B 淋巴细胞在没有外部 Ag 刺激的情况下产生的。它们识别自我、改变的自我和外来的 Ags,构成抵御入侵病原体的重要第一线防御,并作为组织稳态的先天识别受体。已在新生儿和未感染个体中发现天然 IgG Abs。然而,它们的生理作用仍不清楚。以前,没有报道过针对氧化特异性表位的天然 IgG Abs。在这里,我们展示了针对丙二醛乙醛 (MAA) 修饰的低密度脂蛋白的小鼠 IgG mAb 的克隆和表征。序列分析揭示了与种系基因的高度同源性,表明它们是天然的。进一步研究表明,MAA 特异性天然 IgG Abs 与主要牙周病原体发生交叉反应牙龈卟啉单胞菌和识别其主要毒力因子 gingipain Kgp 和长菌毛。该研究提供的证据表明,天然 IgG 可能通过识别和清除入侵病原体和/或修饰的自身抗原,在先天免疫防御和调节组织稳态中发挥重要作用,从而参与牙周炎和动脉粥样硬化的发展。

更新日期:2021-01-16
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