RT Journal Article
SR Electronic
T1 Ig light chains are secreted predominantly as monomers.
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 2969
OP 2975
VO 157
IS 7
A1 Dul, J L
A1 Aviel, S
A1 Melnick, J
A1 Argon, Y
YR 1996
UL http://www.jimmunol.org/content/157/7/2969.abstract
AB 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.