A reactive disulfide bond (SS)* was detected and characterized in IgG of humans, rats and mice by virtue of disulfide interchange with dithionitrobenzoate. (SS)* was found exclusively in human IgG1 and rat IgG2b. In human IgG1 (SS)* was identified as the upper one of the two interheavy bridges in the hinge, where it appears to take part in complement activation. The biological significance of (SS)* in IgG was underlined by the fact that no other serum proteins were found to exhibit a similar reactivity.

Previous studies have shown that human IgG1 contains a ‘reactive’ disulfide bridge (SS*), detectable by a 24-hour disulfide exchange reaction, and that the serum level of this IgG subclass is selectively diminished in patients with various malignant diseases. Here we present evidence that in rats IgG2b is the only subclass that carries one SS* per molecule. Furthermore, it is shown that rats inoculated with experimental tumor lines, i.e., the Yoshida hepatoma ascites tumor and the Walker 256 carcinosarcoma growing in ascites or as solid tumor, exhibit significantly decreased SS* per mole IgG which corresponds to a selective diminution of IgG2b. Although at later stages there is a quantitative correlation with the tumor burden, with the Walker tumor this effect becomes significant as early as 24 h after inoculation, i.e., well before exponential tumor growth and an absolute reduction of total IgG. Control animals injected intraperitoneally with either viable spleen cells or irradiated Walker 256 cells did not show comparable alterations in their IgG subclass profile. Thus, the selective defect of IgG2b requires the presence of viable and proliferating tumor cells. Possible mechanism(s) of tumor-associated shifts in IgG subclasses are discussed.