title: Coordination of immunoglobulin chain folding and immunoglobulin chain assembly is essential for the formation of functional IgG.
abstract: The first constant domain (CH1) of immunoglobulin heavy (H) chains is essential for BiP-mediated retention of unassembled H chains in the endoplasmic reticulum (ER). Here, we demonstrated that both wild-type and a mutant gamma chain lacking the CH1 domain bind BiP when they are reduced in vivo. However, only oxidized mutant H chain dimers are released from BiP interaction, whereas oxidized wild-type gamma chain dimers still bind BiP. In light (L) chain-producing cells, some of the mutant H chains accumulate with L chains in ER-derived vesicles and some are secreted as IgG. Furthermore, only half of the secreted antibodies bind antigen. We found the same with a mutant gamma chain, in which the CH1 domain was replaced by a CH3 domain. Therefore, we propose that BiP interaction with incompletely folded CH1 domains is required to mediate correct assembly of H and L chains.
authors.affiliation: Institut für Biochemie I, Universität Heidelberg, Federal Republic of Germany.
authors.forename: C R
authors.initials: CR
authors.lastname: Kaloff
authors.forename: I G
authors.initials: IG
authors.lastname: Haas
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000737:chemistry; D001666:Binding Sites, Antibody / Q000502:physiology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis; D051379:Mice; D009154:Mutation / Q000235:genetics; D011233:Precipitin Tests; D011487:Protein Conformation; D017510:Protein Folding; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains