Department of Biomedical Sciences, University of Illinois College of Medicine Rockford, Rockford, IL 61107.
Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
J Immunol. 2020 Jul 15;205(2):407-413. doi: 10.4049/jimmunol.2000014. Epub 2020 Jun 10.
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 (HMGB1). 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.
细胞外高迁移率族蛋白 B1（HMGB1）是一种典型的损伤相关分子模式。虽然细胞外 HMGB1 的稳态水平可能有利于免疫防御、组织修复和组织再生，但过多的 HMGB1 与炎症性疾病有关。这就提出了一个有趣的问题：健康的身体如何控制细胞外 HMGB1 的水平？在这项研究中，我们在健康人类和健康小鼠的血浆中鉴定出一种抗 HMGB1 IgM 自身抗体，该抗体通过特异性结合 100%保守表位（即 HMW4，HMGB1）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 同时触发其 BCR 和 TLR4，可刺激抗 HMW4 IgM 的产生。细胞外 HMGB1 诱导自身中和 Ab 的能力表明，在健康的身体中存在一个反馈回路，限制了这种损伤相关分子模式的水平。
