Separation of anti-histone antibodies from nonimmune histone-precipitating serum proteins, predominantly alpha2-macroglobulin.

Calf thymus histories formed precipitates with human, rabbit, guinea pig, mouse, goat, or sheep sera regardless of whether the subjects were immunized with histones. Their order of activity in precipitation was: H4 >H3 >H2a >H2b ? H1. Precipitation occurred with more than one serum protein fraction, but not with purified IgG, IgM, or crystallized albumin. The major nonimmune precipitant had the size and charge properties of α2-macroglobulin. Serological analysis with anti-α2-macroglobulin antiserum confirmed the presence of this protein in the precipitating fractions, and its selective depletion from histone-precipitated serum. Specific anti-histone antibodies were separated from the nonimmune precipitants by DEAE-cellulose chromatography.