Natural antibodies as a sensor of electronegative damage-associated molecular patterns (DAMPs)

Natural antibodies (Abs), predominantly IgMs, play an important function in the host response to the recognition of endogenous danger signals called damage-associated molecular patterns (DAMPs). Many of the natural IgM Abs also show several different antigenic cross-reactivities toward covalently modified proteins, such as oxidized low-density lipoproteins and advanced glycation end products. Of interest, a recent study has shown that these DAMPs have several physicochemical characteristics that differ from native proteins, such as an increased negative charge due to modification of the lysine residues. This finding may provide a mechanistic insight into the multispecificity of the natural Abs. •Natural antibodies, predominantly IgMs, play an important function in the host response to the recognition of damage-associated molecular patterns (DAMPs).•Many of the natural antibodies show several different antigenic cross-reactivities toward covalently modified proteins.•DAMPs have several physicochemical characteristics that differ from native proteins, such as an increased negative charge.•Natural antibodies act as magnets to attract any nearby electronegatively charged DAMPs.