The nature of Bence-Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins.

Abstract

The chemical relations among Bence-Jones proteins, myeloma proteins, and normal gamma-globulins have been investigated by a variety of means. Starch gel electrophoresis in 8 M urea of reduced alkylated Bence-Jones proteins yielded patterns of bands corresponding to those of the light (L) polypeptide chains of the dissociated myeloma protein from the same patient. One instance in which this correspondence was found was chosen for extensive study. Chromatography on carboxymethylcellulose in 6 M urea was employed to isolate the light (L) polypeptide chains and heavy (H) polypeptide chains of the completely reduced and alkylated myeloma protein. Isolation of similarly treated Bence-Jones protein from the same patient corroborated the correspondence to the L chains of the myeloma protein. Amino acid analyses indicated that the compositions of the Bence-Jones protein and the L chains of the myeloma protein were identical. Moreover, the thermosolubility properties and spectrofluorometric behavior of the isolated L chains and Bence-Jones protein were similar. Ultracentrifugal analyses of the L chains of normal human 7S gamma-globulin showed that their molecular weight in 6 M urea was 20,000. In aqueous solution their molecular weight was 41,000, suggesting that they exist as dimers under these conditions. The L chains of normal human gamma-globulin were found to have reversible thermosolubility properties similar to those of Bence-Jones proteins. The H chains of normal human gamma-globulin did not share these properties. Using spectrofluorometric methods, characteristic molecular transitions were found upon heating Bence-Jones proteins and L chains. These transitions were indicated by an increase in the intensity of fluorescence at well defined temperatures as well as by reversible shifts in the wavelength of maximal emission. The findings suggest that Bence-Jones proteins are composed of L chains of the type found in normal and pathological gamma-globu]ins.