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HMGB1-Neutralizing IgM Antibody Is a Normal Component of Blood Plasma
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-10 , DOI: 10.4049/jimmunol.2000014
Yajun Geng 1, 2 , Gnanasekar Munirathinam 1 , Sunil Palani 1 , Joseph E Ross 3 , Bin Wang 4 , Aoshuang Chen 5 , Guoxing Zheng 5
Affiliation  

Key Points Anti-HMGB1 neutralizing IgM autoantibody exists normally in healthy humans and mice. In mice, B-1 cells produce the Ab in response to extracellular HMGB1. Extracellular high-mobility group box 1 (HMGB1) is a prototypic damage-associated molecular pattern. Although a homeostatic level of extracellular HMGB1 may be beneficial for immune defense, tissue repair, and tissue regeneration, excessive HMGB1 is linked to inflammatory diseases. This prompts an intriguing question: how does a healthy body control the level of extracellular HMGB1? In this study, in the plasma of both healthy humans and healthy mice, we have identified an anti-HMGB1 IgM autoantibody that neutralizes extracellular HMGB1 via binding specifically to a 100% conserved epitope, namely HMW4 (HMGB198–112). In mice, this anti-HMW4 IgM is produced by peritoneal B-1 cells, and concomitant triggering of their BCR and TLR4 by extracellular HMGB1 stimulates the production of anti-HMW4 IgM. The ability of extracellular HMGB1 to induce its own neutralizing Ab suggests a feedback loop limiting the level of this damage-associated molecular pattern in a healthy body.

中文翻译:

HMGB1-中和 IgM 抗体是血浆的正常成分

要点 Anti-HMGB1 中和 IgM 自身抗体通常存在于健康人和小鼠中。在小鼠中,B-1 细胞响应细胞外 HMGB1 产生抗体。细胞外高迁移率组框 1 (HMGB1) 是一种原型损伤相关分子模式。尽管细胞外 HMGB1 的稳态水平可能有益于免疫防御、组织修复和组织再生,但过量的 HMGB1 与炎症性疾病有关。这引发了一个有趣的问题:健康的身体如何控制细胞外 HMGB1 的水平?在这项研究中,在健康人和健康小鼠的血浆中,我们鉴定了一种抗 HMGB1 IgM 自身抗体,该抗体通过与 100% 保守表位 HMW4 (HMGB198-112) 特异性结合来中和细胞外 HMGB1。在小鼠中,这种抗 HMW4 IgM 由腹膜 B-1 细胞产生,细胞外 HMGB1 同时触发 BCR 和 TLR4 会刺激抗 HMW4 IgM 的产生。细胞外 HMGB1 诱导其自身中和抗体的能力表明一个反馈回路限制了健康身体中这种与损伤相关的分子模式的水平。
更新日期:2020-06-10
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