Effect of light chain V region duplication on IgG oligomerization and in vivo efficacy.
A human immunoglobulin G1 (IgG1) antibody oligomer was isolated from a transfected myeloma cell line that produced a monoclonal antibody to group B streptococci. Compared to the IgG1 monomer, the oligomer was significantly more effective at protecting neonatal rats from infection in vivo. The oligomer was also shown to cross the placenta and to be stable in neonatal rats. Immunochemical analysis and complementary DNA sequencing showed that the transfected cell line produced two distinct kappa light chains: a normal light chain (Ln) with a molecular mass of 25 kilodaltons and a 37-kilodalton species (L37), the domain composition of which was variable-variable-constant (V-V-C). Cotransfection of vectors encoding the heavy chain and L37 resulted in production of oligomeric IgG.
Shuford
W
W
Department of Immune Sciences, Bristol-Myers Squibb Pharmaceutical Research Institute-Seattle, WA 98121.
Raff
H V
HV
Finley
J W
JW
Esselstyn
J
J
Harris
L J
LJ
D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology / Q000493:pharmacokinetics; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology / Q000493:pharmacokinetics; D002460:Cell Line; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D046911:Macromolecular Substances; D008431:Maternal-Fetal Exchange; D009101:Multiple Myeloma; D011247:Pregnancy; D051381:Rats; D013290:Streptococcal Infections / Q000517:prevention & control; D013292:Streptococcus agalactiae / Q000276:immunology; D014162:Transfection
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D046911:Macromolecular Substances