Identification of Neutralizing Anti-HMGB1 IgM Autoantibody and Its B Cell Producers

Abstract Extracellular High Mobility Group Box 1 (HMGB1) is a prototypic damage-associated molecular pattern (DAMP). While homeostatic level of extracellular HMGB1 may be beneficial for immune defense, tissue repair and regeneration, excessive linked to chronic inflammation inflammatory diseases. This prompts an intriguing question: How does healthy body control the HMGB1? Here we have identified, in plasma both humans mice, anti-HMGB1 IgM autoantibody that neutralizes via binding specifically 100% conserved epitope, namely HMW4 (HMGB1 98–112). In this (i.e., anti-HMW4 IgM) produced by peritoneal B-1 cells, concomitant triggering their B cell receptor toll-like 4 stimulates production IgM. The ability induce its own neutralizing antibody suggests feedback loop limiting DAMP body. Currently, our studies are ongoing identify characterize human counterpart cells produce IgM, first amplifying HMW4-reactive from peripheral blood mononuclear (PBMCs) NSG recipient presence cell-stimulating adjuvants (such as mitogens). These serve prelude exploring down road treating patients with diseases provide insight pertaining role regulation other molecules.