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PMID: 2122454 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A single amino acid substitution in the variable region of the light chain specifically blocks immunoglobulin secretion.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 20 ·1990-10-00 ·Pages 8135-9

Dul JL, Argon Y

Abstract

Although immunoglobulin light chains are usually secreted in association with heavy chains, free light chains can be secreted by lymphocytes. To identify the structural features of light chains that are essential for their secretion, we mutated a conserved sequence in the variable domain of a lambda I light chain. The effects of the mutations on secretion were assayed by transient expression in COS-1 cells. One mutant (AV60), which replaced Ala-60 with Val, was secreted as efficiently as wild-type lambda I by transfected COS-1 cells. This result was not surprising because secreted lambda II chains contain valine in this position. However, a second lambda I mutant (AV60FS62), which replaced Phe-62 with Ser as well as Ala-60 with Val, was not secreted. This mutant was arrested in the endoplasmic reticulum, as judged by immunofluorescence and by its association with a lumenal endoplasmic reticulum protein, immunoglobulin heavy chain binding protein (BiP). The defect in secretion was not due to gross misfolding of the lambda I chain, since cells cotransfected with AV60FS62 and an immunoglobulin heavy chain gene produced functional antigen-binding antibodies. These assembled IgM molecules were still not secreted. Hence, the replacement of Phe-62 with Ser specifically affects a determinant on the lambda I light chain that is necessary for the intracellular transport of this molecule.

MeSH Terms
Animals Cell Line Genes, Immunoglobulin Immunoglobulin Light Chains/genetics Immunoglobulin Variable Region/genetics Mice Models, Structural Mutagenesis, Site-Directed Phenylalanine Plasmacytoma Protein Conformation Restriction Mapping Serine Transfection Valine
Chemicals
Immunoglobulin Light Chains Immunoglobulin Variable Region Serine Phenylalanine Valine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dul J L
Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
Argon Y
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.20.8135
Published
1990-10-00
Pages
8135-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54907
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.87.20.8135 PMC Full Text View journal details
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