Influence of the isotype of the light chain on the properties of IgG.
It is widely appreciated that the isotype of the H chain of the Ab molecule influences its functional properties. We have now investigated the contribution of the isotype of the L chain to the structural and functional properties of the Ab molecule. In these studies, the L chain variable region of a murine anti-dansyl Ab was joined to either human kappa or lambda constant region domains and expressed with mouse-human chimeric H chains of the four human IgG isotypes. The resulting Abs were secreted as fully assembled molecules although, as has been previously observed, IgG4 with either kappa or lambda L chains was also secreted as HL half-molecules. However, the isotype of the L chain can influence the kinetics of intracellular assembly with IgG1lambda, IgG2lambda, and IgG4lambda assembling more slowly than their kappa counterparts. The isotype of the L chain also influenced the susceptibility of the interchain disulfide bonds to attack by reducing agents with variable effects, depending on the isotype of the H chains. For IgG2, but not for IgG1, -3, and -4, the isotype of the L chain influenced the rate of clearance in mice, with IgG2lambda having a shorter in vivo half-life than IgG2kappa. Only slight differences were also observed between lambda and kappa molecules in their kinetics of binding to and dissociation from the hapten dansyl. These studies demonstrate that the isotype of the L chain has only a slight impact on the structural and functional properties of variable region identical Abs.
Montaño
Ramon F
RF
Department of Microbiology, Immunology, and Molecular Genetics, University of California, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
Morrison
Sherie L
SL
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D003167:Complement Activation; D003601:Cytotoxicity Tests, Immunologic; D004229:Dithiothreitol / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000502:physiology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000502:physiology*; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011993:Recombinant Fusion Proteins; D004229:Dithiothreitol