Bence Jones proteins and light chains of immunoglobulins. II. Immunochemical differentiation and classification of kappa-chains.

Three distinct classes of kappa light polypeptide chains have been detected immunochemically by an antiserum (R185) prepared against a kappa Bence Jones protein with a glutamyl amino terminal residue. This antiserum had specificity for kappa light chains with glutamyl amino terminal residues and differentiated kappa-chains with aspartyl amino terminal residues into two classes: the three kappa-chain classes have been designated as kappa(glu), kappa(aspII), and kappa(aspI). The ability of antiserum R185 to detect these antigenic differences on the intact immunoglobulin molecule, as well as on the isolated light chain or Bence Jones protein, made feasible the direct classification of type K myeloma proteins and M-macroglobulins (Waldenström). The multispecificity of the antiserum permitted the quantitation of type kappa(glu) light chains in normal, hypergammaglobulinemic, and hypogammaglobulinemic sera. Whereas the distribution of myeloma proteins and Bence Jones proteins in the kappa(glu) class correlated with the distribution of kappa(glu) chains in normal and hypergammaglobulinemic sera, the M-macroglobulins in the kappa(glu) class represented 90% of the total M-macroglobulins tested and revealed a marked divergence from the range of 24-31% of kappa(glu) immunoglobulins in normal sera. A preponderance of kappa(glu) chains was detected in the sera from patients with non-sex-linked hypogammaglobulinemia and represented 60-77% of the total type K light chain content. The controlled cleavage of a Bence Jones protein representative of each kappa-chain class into its variant half and constant half made possible the localization on the light polypeptide chain, the reactive sites for which antiserum R185 had specificity. The correlations between immunochemical and structural classification of kappa light chains are discussed.