Polyreactive IgM antibodies in the circulation are masked by antigen binding

Human plasma containing IgM showed only minimal, if any, reactivity with a panel of antigens as measured by ELISA. In contrast, affinity-purified IgM showed many times more reactivity with the same panel of antigens. When plasma was added back to the affinity-purified IgM, the reactivity of the IgM with antigens was completely inhibited by undiluted plasma and by as much as 40% with as little as a 1:100 dilution of plasma. When the affinity-purified IgM was affinity-purified a second time by passage through antigen-specific columns (e.g., insulin or Fc or beta-galactosidase), the eluted antibodies bound not only to the antigen used for purification, but also to a panel of unrelated antigens, indicating that the antibodies were polyreactive. It is concluded that polyreactive IgM antibodies are present in the circulation but are masked by binding to circulating antigens.