Normal human serum contains natural antibodies reactive with autologous ABO blood group antigens

It is widely accepted that the serum of healthy individuals contains natura l antibodies only against those blood group A or B antigens that are not ex pressed on the individual's red blood cells. The mechanisms involved in tol erance to autologous blood group antigens remain unclear. In the present st udy, we show that IgM and IgG antibodies reactive with autologous blood gro up antigens are present in the immunoglobulin fraction of normal human seru m, Natural IgG anti-A antibodies purified by affinity chromatography from I gG of individuals of blood group A exhibited an affinity for A trisaccharid e antigen in the micromolar range and agglutinated A red cells at sixfold h igher concentrations than those required for agglutination with affinity-pu rified anti-A IgG of individuals of blood group B, Whereas autoantibodies r eactive with self A and B antigens are readily detected in purified IgG and IgM fractions, their expression is restricted in whole serum as a result o f complementary interactions between variable regions of antibodies, These observations suggest that tolerance to autologous ABO blood group antigens is dependent on peripheral control of antibody autoreactivity, (C) 1999 by The American Society of Hematology.