Ig light chains are secreted predominantly as monomers.
Ig light (L) chains are secreted not only as part of assembled Ab molecules, but also as free L chains, the latter process being involved in the pathology of several diseases. The secretion competence of free L chains distinguishes them from free subunits of other oligomeric proteins, which are usually retained intracellularly. We used several techniques to test the idea that secretion of free L chains is dependent on dimerization. Coexpression of pairs of L chains, differing in only one amino acid, which alters the secretory phenotype, shows that these L chains behave independently: the wild-type chains are secreted, whereas the mutants are retained intracellularly. A survey of kappa- or lambda-producing cell lines by nonreducing gel electrophoresis shows that a negligible fraction of these L chains exists as disulfide-bonded dimers. Moreover, chemical cross-linking and density gradient centrifugation demonstrate that there is no significant pool of noncovalent L chain dimers. Noncovalent heterodimers can be detected readily between a kappa-chain and a chimera consisting of a heavy chain variable domain linked to the kappa-chain constant domain. This confirms that noncovalent L chain homodimers would have been detected if they were present. These findings about the association state of free L chains are independent of the host cell, as they are observed in both myeloma cells and COS fibroblasts. We conclude that L chain dimerization is a rare event that neither facilitates secretion nor is required for it.
Dul
J L
JL
Department of Pathology, University of Chicago, IL 60637, USA.
Aviel
S
S
Melnick
J
J
Argon
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002461:Cell Line, Transformed; D002499:Centrifugation, Density Gradient; D002522:Chlorocebus aethiops; D003553:Cystine / Q000032:analysis; D005347:Fibroblasts / Q000737:chemistry; D007142:Immunoglobulin gamma-Chains / Q000737:chemistry; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009194:Myeloma Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007142:Immunoglobulin gamma-Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D009194:Myeloma Proteins; D011993:Recombinant Fusion Proteins; D003553:Cystine