Bence-Jones Proteins and Light Chains of Inununoglobulins

The primary structure of Bence-Jones proteins is characterized by a variable amino acid sequence in the aminoterminal half and a constant amino acid sequence in the carboxyl-terminal half. Proteins corresponding either to the variant half or to the constant half of whole Bence-Jones proteins have been detected in urine of patients with multiple myeloma. Both halves of a Bence-Jones protein were detected in the urine of one patient, and in another patient the constant half of a Bence-Jones protein was found in serum as well as urine. Metabolic studies indicated that the variant half and the constant half can result from catabolism of the whole molecule, and biosynthetic studies suggested that the variant and constant halves may also have synthetic origin. Bence-Jones proteins and light chains isolated from Gor A-myeloma proteins were cleaved in vitro into the variant half and the constant half. Cleavage was initiated by a proteolytic factor in urine as well as by several types of endopeptidases, and definitive immunochemical identification of the cleaved products as variant half and constant half required development of specific antisera. Particular susceptibility to proteolysis of the peptide bond between the variant half and constant half of Bence-Jones proteins and between the variant half and constant half of light chains provides the first direct evidence for the presence of an exposed area in the switch region of these molecules. The ability to cleave specifically Bence-Jones proteins and light chains makes possible the preparation and isolation of variant halves and constant halves in quantities sufficient for studies of the individual properties of each half. Studies on the isolated variant halves and constant halves of BenceJones proteins indicated that the variant half was more resistant to proteolysis than the constant half, was crystallizable, and had thermal solubility behavior identical with that of the intact BenceJones protein.