Human myeloma IgA half-molecules.

AUTOR(ES)

Spiegelberg, H L

RESUMO

A lambda, IgAl myeloma protein that formed two chain half-molecules was obtained from a patient who had typical multiple myeloma. His serum contained 1.3 g/100 ml of an IgA paraprotein of gamma-1 electrophoretic mobility, his urine predominantly lambda Bence Jones protein, and only small amounts of IgA paraprotein. Analytical ultracentrifugation of the isolated serum IgA protein showed 7.0S and 4.5S protein peaks but no IgA polymers. When the 7.0S and 4.5S protein peaks were tested with an antiserum specific for alpha chain, both fractions were antigenically deficient compared to control IgA myeloma proteins but showed a line of identity to their F(ab')2 fragments. The serum and 7.0S protein fraction showed double precipitin lines in IgA radial immunodiffusion plates and in immunoelectrophoretic analysis, one line being formed by the myeloma protein and the other by residual normal IgA. The myeloma protein did not form a precipitin line with antisera specific for the IgA Fc fragment. Sodium dodecylsulfate-urea-polyacrylamide gel electrophoresis demonstrated that both the 7.0S and 4.5S fractions of the myeloma protein consisted of covalently linked heavy and light chains, 4.5S fraction being apparently the half-molecule of the 7.0S protein. The heavy chain had a mol wt of 46,500 daltons compared to 55,000 daltons for normal alpha chains. Reduction and alkylation in aqueous solutions resulted in dissociation of the 7.0S myeloma protein fractions into smaller units, probably half-molecules, suggesting that the noncovalent interactions between the alpha chains were substantially weakened or absent, presumably as a result of a deletion in the Fc portion of the alpha chain. The catabolic rates of the radio-labeled 7.0S and 4.5S protein in rhesus monkeys were similar to those of control IgA myeloma proteins; the excretion of protein-bound radioactivity of the IgA half-molecules into the urine was no greater than that of the 7.0S or of control IgA myeloma proteins. It is suggested that the myeloma IgA half-molecule is probably derived from an IgAl mutant that is carried in the human genome and that it is unlikely a representative of a rare IgA subclass or an IgA l allotypic variant.

Documentos Relacionados

• Human myeloma IgG half-molecules. Catabolism and biological properties.
• Differential Susceptibility of Human IgA Immunoglobulins to Streptococcal IgA Protease
• Covalent Joining of Phenylalanine Transfer Ribonucleic Acid Half-Molecules by T4 RNA Ligase
• Recombinant human IgA expressed in insect cells.
• Partial Duplication in the “Hinge” Region of IgA1 Myeloma Proteins