Polymeric Forms of Free Normal κ and λ Chains of Human Immunoglobulin

Abstract

Abstract Physical, chemical, and immunological properties and association-dissociation behavior of various molecular forms of free normal light chains of human immunoglobulin have been examined. Free light chains were isolated from the urine of both normal individuals and patients with tubular proteinuria by means of ultrafiltration, zone electrophoresis, gel chromatography, and ion exchange chromatography. The yield of purified chains from each liter of pooled normal urine was, on the average, 0.7 mg (approximately 20% of the amount present). The quantities obtained from the patients were 4 to 30 times higher. Examinations by ultracentrifugation, gel chromatography, and starch gel electrophoresis in nondissociating and in dissociating media revealed that light chains from the two sources consisted of monomers, noncovalently linked dimers, covalently linked dimers, and tetramers. The various species showed some tendency to associate and (or) dissociate. Free chains from the patients had a relatively high content of dimers and tetramers. Immunological examinations and amino acid analyses indicated higher ratios of κ chain to λ chain in noncovalently linked dimers and monomers than in covalently linked dimers. In the dimers, there was a highly specific pairing of chains with the same antigenic type and, apparently, the same or similar electrophoretic mobility. The above results, in conjunction with values for the sedimentation coefficients, Stokes' radii, diffusion coefficients, molecular weights, and frictional ratios, provide strong support for a previous suggestion that free normal light chains of human immunoglobulin are counterparts to Bence-Jones proteins.