Abstract
Hybrid cells secreting one, two, or three different immunoglobulins were constructed. The loss of immunoglobulin heavy or light chain expression was monitored. Chain loss was random only in lines with an excess of active light chain genes over heavy chain genes. In all other combinations preferential heavy chain loss was observed. Variant cells altered in heavy or light chain synthesis exhibited an altered chain loss pattern. It is therefore proposed that free immunoglobulin heavy chain is toxic for the cells. The interdependence of the two gene products gives a possible molecular explanation of apparent directed chromosome loss in hybrid cells.
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- Baumal R., Scharff M. D. Synthesis, assembly and secretion of gamma-globulin by mouse myeloma cells. V. Balanced and unbalanced synthesis of heavy and light chains by IgG-producing tumors and cell lines. J Immunol. 1973 Aug;111(2):448–456. [PubMed] [Google Scholar]
- Burrows P., LeJeune M., Kearney J. F. Evidence that murine pre-B cells synthesise mu heavy chains but no light chains. Nature. 1979 Aug 30;280(5725):838–840. doi: 10.1038/280838a0. [DOI] [PubMed] [Google Scholar]
- Coffino P., Scharff M. D. Rate of somatic mutation in immunoglobulin production by mouse myeloma cells. Proc Natl Acad Sci U S A. 1971 Jan;68(1):219–223. doi: 10.1073/pnas.68.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cowan N. J., Secher D. S., Milstein C. Intracellular immunoglobulin chain synthesis in non-secreting variants of a mouse myeloma: detection of inactive light-chain messenger RNA. J Mol Biol. 1974 Dec 25;90(4):691–701. doi: 10.1016/0022-2836(74)90533-6. [DOI] [PubMed] [Google Scholar]
- Franklin E. C., Frangione B. Structural variants of human and murine immunoglobulins. Contemp Top Mol Immunol. 1975;4:89–126. doi: 10.1007/978-1-4615-8930-3_4. [DOI] [PubMed] [Google Scholar]
- Hengartner H., Meo T., Müller E. Assignment of genes for immunoglobulin kappa and heavy chains to chromosomes 6 and 12 in mouse. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4494–4498. doi: 10.1073/pnas.75.9.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Köhler G., Pearson T., Milstein C. Fusion of T and B cells. Somatic Cell Genet. 1977 May;3(3):303–312. doi: 10.1007/BF01538748. [DOI] [PubMed] [Google Scholar]
- Morrison S. L. Murine heavy chain disease. Eur J Immunol. 1978 Mar;8(3):194–199. doi: 10.1002/eji.1830080311. [DOI] [PubMed] [Google Scholar]
- Morrison S. L., Scharff M. D. Heavy chain-producing variants of a mouse myeloma cell line. J Immunol. 1975 Feb;114(2 Pt 1):655–659. [PubMed] [Google Scholar]
- Shulman M. J., Köhler G. Immunoglobulin mu and gamma heavy chain classes are not determined by class-specific RNA-splicing enzymes. Nature. 1978 Aug 31;274(5674):917–919. doi: 10.1038/274917a0. [DOI] [PubMed] [Google Scholar]
- Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]