Analysis of the normal human IgG antibody repertoire. Evidence that IgG autoantibodies of healthy adults recognize a limited and conserved set of protein antigens in homologous tissues.

We have used a quantitative immunoblot technique to analyze the Ab repertoire of IgG in the serum of healthy adults with a large panel of homologous and foreign Ags in tissue extracts. Densitometric patterns of reactivity of purified IgG with self-Ags exhibited striking homogeneity among individuals with regard to the protein bands that were recognized. Purified IgG showed higher levels of reactivity with self-Ags than IgG in whole serum. Reactivity with self-Ags of IgG in whole serum was restricted to a small number of protein bands (fewer than 10). There were significant inter-individual differences in the intensity and nature of immunoreactivities. Purified IgG of different individuals exhibited heterogeneous patterns of immunoreactivity with Ags in bacterial extracts. Comparative analysis of repertoires of IgG and IgM indicated that all protein Ags recognized by IgM were also reactive with purified IgG. Some proteins in homologous and in foreign tissue extracts reacted solely with IgG. Our observations provide direct evidence for the restricted and conserved character of the antiself-repertoire of IgG of healthy adults and suggest that natural IgG Ab repertoires in serum are specifically selected for reactivity with a limited set of self-Ags. In addition, IgG autoreactivity in whole serum is controlled by non-IgG factors that determine the unique reactivity pattern of each individual.