Natural anti-IgG antibodies to autologous and heterologous species IgG

In the present report we have isolated by affinity chromatography a putative human Fab₂ that binds to human Fab₂. We have examined the binding specificity of the Fab₂ anti-Fab₂ to IgG, Fab₂, Fab, and Fc fragments derived from various species IgG and have attempted to isolate species-specific antibody by affinity chromatography. The results obtained in this study using ¹²⁵I-Fab₂ anti-Fab₂ demonstrate that the natural antihuman antibodies cannot be separated into IgG species-specific population. Moreover, subjecting affinity-isolated Fab₂ anti-Fab₂ to a Sepharose 4B-mouse IgG column failed to remove mouse IgG-specific binding activity. These data suggest that the human natural antibodies, ie, Fab₂ anti-Fab₂ recognize homology epitopes (domain) and not species-specific IgG epitopes. The observation that Fab₂ anti-Fab₂ reacts with the Fc fragment as well as Fab supports this hypothesis. Additionally, the binding specificity of the Fab₂ that was bound (fractions 30-35) by the Sepharose 4B-mouse IgG column exhibited the same reactivity as the nonbound fractions 5,6. The observation that Fab₂ that were bound by the Sepharose 4B-mouse IgG suggest that this population contained molecules with higher binding affinities than the Fab₂ in fractions 5,6.