IgG molecules are exposed on a regular basis to acidic conditions during immunoaffinity purification procedures, as well as during the production of some therapeutic
immunoglobulin preparations. This exposure is known to induce in them an
antigen-binding polyreactivity. The molecular mechanisms and the possible biological significance of this phenomenon remain, however, poorly understood. In addition to the previously reported ability of these modified
IgG antibodies to interact with a large panel of
self-antigens, enhanced binding to non-
self-antigens (bacterial), an increased ability to engage in F(ab')(2)/F(ab')(2) (idiotype/anti-idiotype) interactions and an increased functional
antigen-binding affinity are reported here. The newly acquired 'induced polyreactivity' of low-pH
buffer-exposed
IgG is related to structural changes in the
immunoglobulin molecules, and is at least partly attributable to the enhanced role of the hydrophobic effect in their interactions with
antigen. Our results suggest that data from many previous studies on monoclonal and polyclonal
IgG antibodies purified by low-pH
buffer elution from
protein A or
protein G immunoaffinity columns should be reconsidered, as the procedure itself may have dramatically affected their
antigen-binding behavior and biological activity. Low-pH
buffer-treated pooled therapeutic
immunoglobulins acquire novel beneficial properties, as passive immunotherapy with the pH 4.0
buffer-exposed, but not with the native therapeutic
intravenous immunoglobulin preparation, improves the survival of mice with bacterial
lipopolysaccharide-induced
septic shock.