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. 1992 Apr;11(4):1573–1581. doi: 10.1002/j.1460-2075.1992.tb05202.x

Interaction of BiP with newly synthesized immunoglobulin light chain molecules: cycles of sequential binding and release.

M R Knittler 1, I G Haas 1
PMCID: PMC556606  PMID: 1563355

Abstract

Here we show that not only transport defective but all immunoglobulin light chains interact with BiP. Association of BiP with its ligand takes place during or shortly after translation of the light chains. The biological half life of the BiP-light chain complex depends on the fate of the light chains. Light chains which are secreted interact with BiP for only a very short time. In contrast, the complex is biologically more stable in cells which do not secrete their L chains. In these cells, dissociation from BiP correlates with the biological half life of the L chains arguing for a degradation pathway in the endoplasmic reticulum. Instead of being degraded in association with its ligand, BiP is released from the complex and binds to newly synthesized polypeptides. These results support the notion that both H and L chains require the chaperoning function of BiP before or during the process of antibody assembly.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baumal R., Birshtein B. K., Coffino P., Scharff M. D. Mutations in immunoglobulin-producing mouse myeloma cells. Science. 1973 Oct 12;182(4108):164–166. doi: 10.1126/science.182.4108.164. [DOI] [PubMed] [Google Scholar]
  2. Blount P., Merlie J. P. BIP associates with newly synthesized subunits of the mouse muscle nicotinic receptor. J Cell Biol. 1991 Jun;113(5):1125–1132. doi: 10.1083/jcb.113.5.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bole D. G., Hendershot L. M., Kearney J. F. Posttranslational association of immunoglobulin heavy chain binding protein with nascent heavy chains in nonsecreting and secreting hybridomas. J Cell Biol. 1986 May;102(5):1558–1566. doi: 10.1083/jcb.102.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braakman I., Hoover-Litty H., Wagner K. R., Helenius A. Folding of influenza hemagglutinin in the endoplasmic reticulum. J Cell Biol. 1991 Aug;114(3):401–411. doi: 10.1083/jcb.114.3.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dorner A. J., Bole D. G., Kaufman R. J. The relationship of N-linked glycosylation and heavy chain-binding protein association with the secretion of glycoproteins. J Cell Biol. 1987 Dec;105(6 Pt 1):2665–2674. doi: 10.1083/jcb.105.6.2665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dul J. L., Argon Y. A single amino acid substitution in the variable region of the light chain specifically blocks immunoglobulin secretion. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8135–8139. doi: 10.1073/pnas.87.20.8135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ellis J. Proteins as molecular chaperones. 1987 Jul 30-Aug 5Nature. 328(6129):378–379. doi: 10.1038/328378a0. [DOI] [PubMed] [Google Scholar]
  8. Förster I., Gu H., Rajewsky K. Germline antibody V regions as determinants of clonal persistence and malignant growth in the B cell compartment. EMBO J. 1988 Dec 1;7(12):3693–3703. doi: 10.1002/j.1460-2075.1988.tb03251.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gething M. J., McCammon K., Sambrook J. Expression of wild-type and mutant forms of influenza hemagglutinin: the role of folding in intracellular transport. Cell. 1986 Sep 12;46(6):939–950. doi: 10.1016/0092-8674(86)90076-0. [DOI] [PubMed] [Google Scholar]
  10. Haas I. G., Wabl M. R. Immunoglobulin heavy chain toxicity in plasma cells is neutralized by fusion to pre-B cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7185–7188. doi: 10.1073/pnas.81.22.7185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haas I. G., Wabl M. Immunoglobulin heavy chain binding protein. Nature. 1983 Nov 24;306(5941):387–389. doi: 10.1038/306387a0. [DOI] [PubMed] [Google Scholar]
  12. Hendershot L. M. Immunoglobulin heavy chain and binding protein complexes are dissociated in vivo by light chain addition. J Cell Biol. 1990 Sep;111(3):829–837. doi: 10.1083/jcb.111.3.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hurtley S. M., Helenius A. Protein oligomerization in the endoplasmic reticulum. Annu Rev Cell Biol. 1989;5:277–307. doi: 10.1146/annurev.cb.05.110189.001425. [DOI] [PubMed] [Google Scholar]
  14. Kassenbrock C. K., Garcia P. D., Walter P., Kelly R. B. Heavy-chain binding protein recognizes aberrant polypeptides translocated in vitro. Nature. 1988 May 5;333(6168):90–93. doi: 10.1038/333090a0. [DOI] [PubMed] [Google Scholar]
  15. Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
  16. Kessler S. W. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
  17. Klausner R. D., Sitia R. Protein degradation in the endoplasmic reticulum. Cell. 1990 Aug 24;62(4):611–614. doi: 10.1016/0092-8674(90)90104-m. [DOI] [PubMed] [Google Scholar]
  18. Köhler G., Hengartner H., Shulman M. J. Immunoglobulin production by lymphocyte hybridomas. Eur J Immunol. 1978 Feb;8(2):82–88. doi: 10.1002/eji.1830080203. [DOI] [PubMed] [Google Scholar]
  19. Köhler G., Howe S. C., Milstein C. Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines. Eur J Immunol. 1976 Apr;6(4):292–295. doi: 10.1002/eji.1830060411. [DOI] [PubMed] [Google Scholar]
  20. Köhler G., Milstein C. Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur J Immunol. 1976 Jul;6(7):511–519. doi: 10.1002/eji.1830060713. [DOI] [PubMed] [Google Scholar]
  21. Ma J., Kearney J. F., Hendershot L. M. Association of transport-defective light chains with immunoglobulin heavy chain binding protein. Mol Immunol. 1990 Jul;27(7):623–630. doi: 10.1016/0161-5890(90)90004-j. [DOI] [PubMed] [Google Scholar]
  22. Machamer C. E., Doms R. W., Bole D. G., Helenius A., Rose J. K. Heavy chain binding protein recognizes incompletely disulfide-bonded forms of vesicular stomatitis virus G protein. J Biol Chem. 1990 Apr 25;265(12):6879–6883. [PubMed] [Google Scholar]
  23. Munro S., Pelham H. R. An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell. 1986 Jul 18;46(2):291–300. doi: 10.1016/0092-8674(86)90746-4. [DOI] [PubMed] [Google Scholar]
  24. Nakaki T., Deans R. J., Lee A. S. Enhanced transcription of the 78,000-dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1). Mol Cell Biol. 1989 May;9(5):2233–2238. doi: 10.1128/mcb.9.5.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ng D. T., Hiebert S. W., Lamb R. A. Different roles of individual N-linked oligosaccharide chains in folding, assembly, and transport of the simian virus 5 hemagglutinin-neuraminidase. Mol Cell Biol. 1990 May;10(5):1989–2001. doi: 10.1128/mcb.10.5.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Oi V. T., Morrison S. L., Herzenberg L. A., Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. doi: 10.1073/pnas.80.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pelham H. R. Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell. 1986 Sep 26;46(7):959–961. doi: 10.1016/0092-8674(86)90693-8. [DOI] [PubMed] [Google Scholar]
  28. Sitia R., Neuberger M. S., Milstein C. Regulation of membrane IgM expression in secretory B cells: translational and post-translational events. EMBO J. 1987 Dec 20;6(13):3969–3977. doi: 10.1002/j.1460-2075.1987.tb02739.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Suzuki C. K., Bonifacino J. S., Lin A. Y., Davis M. M., Klausner R. D. Regulating the retention of T-cell receptor alpha chain variants within the endoplasmic reticulum: Ca(2+)-dependent association with BiP. J Cell Biol. 1991 Jul;114(2):189–205. doi: 10.1083/jcb.114.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]

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