Serum decay and placental transport of a mutant mouse myeloma immunoglobulin with defective polypeptide and oligosaccharide structure

A mutant mouse myeloma cell line, M3.11, has been previously isolated from an IgG2b-producing wild type. The immunoglobulin (Ig) produced by M3.11 has been shown in other studies to have the following structural defects: 1) deletion of the Cγ3 domain; 2) failure to glycosylate 30 to 40% of its secreted heavy (H) chains; and 3) a block in assembly with approximately equal amounts of whole molecule (H₂L₂) and half-molecule (HL) being secreted. In addition, the sialic acid content of the wild type and the mutant is similar and minimal. Experiments comparing two biologic functions of these Ig demonstrated that M3.11 had a markedly increased serum decay and a more rapid placental transport than the wild type. The three distinct M3.11 species, H₂L₂, nonglycosylated HL, and glycosylated HL, all had indistinguishable serum half-lives. In addition, M3.11 in vitro exhibited an increased sensitivity to trypsin and a more acidic pI than the wild type. These results support several conclusions regarding the structural features influencing Ig serum decay. Firstly, the serum decay and placental transport of Ig seem to be determined by the H chain polypeptide and not by the presence or absence of carbohydrate in general or of sialic acid in particular. Secondly, those aspects of protein structure that do influence serum decay are not restricted to a single domain but probably represent a complex interaction of multiple sites on the Ig molecule.