The Role of the Kidney in the Catabolism of Bence Jones Proteins and Immunoglobulin Fragments

The role of the kidney in the catabolism of Bence Jones proteins, intact IgG molecules, and isolated L chains, Fab and Fc fragments of IgG, was studied. The proteins were purified, radioiodinated, and their survival times measured in nephrectomized, ureter-severed, and control mice. Active endogenous catabolism was the major factor in overall Bence Jones metabolism since excretion as proteinuria accounted for less than 25% of the total metabolism. The survival times of lambda- and kappa-type human Bence Jones proteins and the Bence Jones protein produced by mice with MPC-2 plasma cell tumor were exceedingly short in both unoperated and ureter-severed mice, with 50% of the injected protein catabolized in from 0.8-1.6 hr. In contrast, the survival of Bence Jones protein was markedly prolonged in nephrectomized animals, with 50% of the injected dose catabolized in from 9 to 17 hr. This ten-fold decrease in catabolic rate indicates that the kidneys are the major site of breakdown of Bence Jones proteins. Similar studies with other proteins indicated that the kidneys are also the major site for catabolism of isolated L chains but not of intact IgG molecules. The Fc immunoglobulin fragment was not catabolized and the Fab fragment only partially catabolized by the kidney. When ureter-severed animals were allowed to develop advanced uremia before being studied, the survival of Bence Jones protein was greatly prolonged, indicating that the catabolic process is impaired in the presence of uremia. The nature of this renal catabolism remains unknown. These observations suggest that the Bence Jones proteins and L chains observed in the urine of patients may reflect only a small fraction of such molecules synthesized by these patients. Furthermore, they provide an explanation for the prolongation of Bence Jones protein survival and the development of Bence Jones proteinemia observed in subjects with multiple myeloma and impaired renal function.