Structural and Biosynthetic Studies of a Human IgA Half Molecule

Abstract

Abstract The serum and urine of a patient with plasma cell leukemia contained free λ light chains and a 4S protein with both α1 and λ antigenic determinants. When isolated from urine, the IgA-related protein was shown to have a substantial antigenic deficiency in the Fc region and to be composed of a single light chain and a single heavy chain. In polyacrylamide gel electrophoresis with sodium dodecylsulfate and 2-mercaptoethanol, the heavy chain appeared to be 13,000 daltons smaller than the usual IgA heavy chain. The molecule lacked methionine, two residues of which are invariant in the C-terminal region of other α chains. The size of the heavy chain, its antigenic deficiency, and its chemical composition were therefore consistent with a deletion of the C-terminal domain. In short-term culture with 3H-leucine, the patient's peripheral plasma cells synthesized a molecule that was antigenically identical to the urine IgA. The mole cules synthesized in vitro appeared similar in size to those of the urine IgA as determined by gel filtration studies in aqueous media. Polyacrylamide gel electrophoresis and autofluorography of newly synthesized molecules isolated immunologically from both culture fluid and cell lysate showed the heavy and light chains to be the same size as those of the urine IgA. These findings are consistent with this abnormal IgA molecule's being synthesized with a deletion in the carboxyl-terminus of the α chain.