Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1983 Nov 11;11(21):7471–7485. doi: 10.1093/nar/11.21.7471

Nucleotide sequences of immunoglobulin mu heavy chain deletion mutants.

W O Baczynsky, S Sugii, H Murialdo, N Pennell, C Filkin, N Hozumi, M J Shulman
PMCID: PMC326496  PMID: 6316263

Abstract

Mutants of an IgM producing hybridoma cell line were isolated which produce mu heavy chain fragments. Two such mutants were found to have internal deletions in the mu gene and the nucleotide sequence of the deletion endpoints was determined. No evidence was found for a role of the heavy chain switch region in the formation of these deletions. The implications of these mutants in defining the requirements of immunoglobulin gene expression are discussed.

Full text

PDF
7471

Images in this article

7474Image
on p.7474
7475Image
on p.7475
7477Image
on p.7477
7478Image
on p.7478

Selected References

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

  1. Adams J. M., Kemp D. J., Bernard O., Gough N., Webb E., Tyler B., Gerondakis S., Cory S. Organization and expression of murine immunoglobulin genes. Immunol Rev. 1981;59:5–32. doi: 10.1111/j.1600-065x.1981.tb00454.x. [DOI] [PubMed] [Google Scholar]
  2. Albertini A. M., Hofer M., Calos M. P., Miller J. H. On the formation of spontaneous deletions: the importance of short sequence homologies in the generation of large deletions. Cell. 1982 Jun;29(2):319–328. doi: 10.1016/0092-8674(82)90148-9. [DOI] [PubMed] [Google Scholar]
  3. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  4. Becker A., Gold M. Isolation of the bacteriophage lambda A-gene protein. Proc Natl Acad Sci U S A. 1975 Feb;72(2):581–585. doi: 10.1073/pnas.72.2.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  6. Benyajati C., Place A. R., Wang N., Pentz E., Sofer W. Deletions at intervening sequence splice sites in the alcohol dehydrogenase gene of Drosophila. Nucleic Acids Res. 1982 Nov 25;10(22):7261–7272. doi: 10.1093/nar/10.22.7261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Calame K., Rogers J., Early P., Davis M., Livant D., Wall R., Hood L. Mouse Cmu heavy chain immunoglobulin gene segment contains three intervening sequences separating domains. Nature. 1980 Apr 3;284(5755):452–455. doi: 10.1038/284452a0. [DOI] [PubMed] [Google Scholar]
  8. Clewell D. B. Nature of Col E 1 plasmid replication in Escherichia coli in the presence of the chloramphenicol. J Bacteriol. 1972 May;110(2):667–676. doi: 10.1128/jb.110.2.667-676.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cullen B. R., Kopchick J. J., Stacey D. W. Effect of intron size on splicing efficiency in retroviral transcripts. Nucleic Acids Res. 1982 Oct 11;10(19):6177–6190. doi: 10.1093/nar/10.19.6177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dunnick W., Rabbitts T. H., Milstein C. An immunoglobulin deletion mutant with implications for the heavy-chain switch and RNA splicing. Nature. 1980 Aug 14;286(5774):669–675. doi: 10.1038/286669a0. [DOI] [PubMed] [Google Scholar]
  11. Eckhardt L. A., Tilley S. A., Lang R. B., Marcu K. B., Birshtein B. K. DNA rearrangements in MPC-11 immunoglobulin heavy chain class-switch variants. Proc Natl Acad Sci U S A. 1982 May;79(9):3006–3010. doi: 10.1073/pnas.79.9.3006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  13. Goldberg G. I., Vanin E. F., Zrolka A. M., Blattner F. R. Sequence of the gene for the constant region of the mu chain of Balb/c mouse immunoglobulin. Gene. 1981 Oct;15(1):33–42. doi: 10.1016/0378-1119(81)90102-5. [DOI] [PubMed] [Google Scholar]
  14. Gough N. M., Kemp D. J., Tyler B. M., Adams J. M., Cory S. Intervening sequences divide the gene for the constant region of mouse immunoglobulin mu chains into segments, each encoding a domain. Proc Natl Acad Sci U S A. 1980 Jan;77(1):554–558. doi: 10.1073/pnas.77.1.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Greenberg R., Lang R. B., Diamond M. S., Marcu K. B. A switch region inversion contributes to the aberrant rearrangement of a mu immunoglobulin heavy chain gene in MPC-11 cells. Nucleic Acids Res. 1982 Dec 11;10(23):7751–7761. doi: 10.1093/nar/10.23.7751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  17. Hawley R. G., Shulman M. J., Murialdo H., Gibson D. M., Hozumi N. Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7425–7429. doi: 10.1073/pnas.79.23.7425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Honjo T., Nakai S., Nishida Y., Kataoka T., Yamawaki-Kataoka Y., Takahashi N., Obata M., Shimizu A., Yaoita Y., Nikaido T. Rearrangements of immunoglobulin genes during differentiation and evolution. Immunol Rev. 1981;59:33–67. doi: 10.1111/j.1600-065x.1981.tb00455.x. [DOI] [PubMed] [Google Scholar]
  19. Hozumi N., Hawley R. G., Murialdo H. Molecular cloning of an immunoglobulin kappa constant gene from NZB mouse. Gene. 1981 Mar;13(2):163–172. doi: 10.1016/0378-1119(81)90005-6. [DOI] [PubMed] [Google Scholar]
  20. Hozumi N., Wu G. E., Murialdo H., Roberts L., Vetter D., Fife W. L., Whiteley M., Sadowski P. RNA splicing mutation in an aberrantly rearranged immunoglobulin lambda I gene. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7019–7023. doi: 10.1073/pnas.78.11.7019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hurwitz J. L., Coleclough C., Cebra J. J. CH gene rearrangements in IgM-bearing B cells and in the normal splenic DNA component of hybridomas making different isotypes of antibody. Cell. 1980 Nov;22(2 Pt 2):349–359. doi: 10.1016/0092-8674(80)90345-1. [DOI] [PubMed] [Google Scholar]
  22. Johnson A. D., Barkan A., Mertz J. E. Nucleotide sequence analysis of the recombinant joints in 16 naturally arising deletion mutants of simian virus 40. Virology. 1982 Dec;123(2):464–469. doi: 10.1016/0042-6822(82)90281-1. [DOI] [PubMed] [Google Scholar]
  23. Khoury G., Gruss P., Dhar R., Lai C. J. Processing and expression of early SV40 mRNA: a role for RNA conformation in splicing. Cell. 1979 Sep;18(1):85–92. doi: 10.1016/0092-8674(79)90356-8. [DOI] [PubMed] [Google Scholar]
  24. Klein G. Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell. 1983 Feb;32(2):311–315. doi: 10.1016/0092-8674(83)90449-x. [DOI] [PubMed] [Google Scholar]
  25. Köhler G., Potash M. J., Lehrach H., Shulman M. J. Deletions in immunoglobulin mu chains. EMBO J. 1982;1(5):555–563. doi: 10.1002/j.1460-2075.1982.tb01208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Leder P., Tiemeier D., Enquist L. EK2 derivatives of bacteriophage lambda useful in the cloning of DNA from higher organisms: the lambdagtWES system. Science. 1977 Apr 8;196(4286):175–177. doi: 10.1126/science.322278. [DOI] [PubMed] [Google Scholar]
  27. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  28. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  29. Marvo S. L., King S. R., Jaskunas S. R. Role of short regions of homology in intermolecular illegitimate recombination events. Proc Natl Acad Sci U S A. 1983 May;80(9):2452–2456. doi: 10.1073/pnas.80.9.2452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mather E. L., Perry R. P. Transcriptional regulation of immunoglobulin V genes. Nucleic Acids Res. 1981 Dec 21;9(24):6855–6867. doi: 10.1093/nar/9.24.6855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  32. Morrison S. L., Scharff M. D. Mutational events in mouse myeloma cells. Crit Rev Immunol. 1981 Sep;3(1):1–22. [PubMed] [Google Scholar]
  33. Murialdo H. Early intermediates in bacteriophage lambda prohead assembly. Virology. 1979 Jul 30;96(2):341–367. doi: 10.1016/0042-6822(79)90094-1. [DOI] [PubMed] [Google Scholar]
  34. Nikaido T., Nakai S., Honjo T. Switch region of immunoglobulin Cmu gene is composed of simple tandem repetitive sequences. Nature. 1981 Aug 27;292(5826):845–848. doi: 10.1038/292845a0. [DOI] [PubMed] [Google Scholar]
  35. Nottenburg C., Weissman I. L. Cmu gene rearrangement of mouse immunoglobulin genes in normal B cells occurs on both the expressed and nonexpressed chromosomes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):484–488. doi: 10.1073/pnas.78.1.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Perry R. P., Kelley D. E., Coleclough C., Seidman J. G., Leder P., Tonegawa S., Matthyssens G., Weigert M. Transcription of mouse kappa chain genes: implications for allelic exclusion. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1937–1941. doi: 10.1073/pnas.77.4.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  38. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schibler U., Marcu K. B., Perry R. P. The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells. Cell. 1978 Dec;15(4):1495–1509. doi: 10.1016/0092-8674(78)90072-7. [DOI] [PubMed] [Google Scholar]
  40. Sharp P. A. Speculations on RNA splicing. Cell. 1981 Mar;23(3):643–646. doi: 10.1016/0092-8674(81)90425-6. [DOI] [PubMed] [Google Scholar]
  41. Shulman M. J., Heusser C., Filkin C., Köhler G. Mutations affecting the structure and function of immunoglobulin M. Mol Cell Biol. 1982 Sep;2(9):1033–1043. doi: 10.1128/mcb.2.9.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  43. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  44. Van Beveren C., van Straaten F., Galleshaw J. A., Verma I. M. Nucleotide sequence of the genome of a murine sarcoma virus. Cell. 1981 Nov;27(1 Pt 2):97–108. doi: 10.1016/0092-8674(81)90364-0. [DOI] [PubMed] [Google Scholar]
  45. Van Ness B. G., Weigert M., Coleclough C., Mather E. L., Kelley D. E., Perry R. P. Transcription of the unrearranged mouse C kappa locus: sequence of the initiation region and comparison of activity with a rearranged V kappa-C kappa gene. Cell. 1981 Dec;27(3 Pt 2):593–602. doi: 10.1016/0092-8674(81)90401-3. [DOI] [PubMed] [Google Scholar]
  46. Young P. R., Scott R. W., Hamer D. H., Tilghman S. M. Construction and expression in vivo of an internally deleted mouse alpha-fetoprotein gene: presence of a transcribed Alu-like repeat within the first intervening sequence. Nucleic Acids Res. 1982 May 25;10(10):3099–3116. doi: 10.1093/nar/10.10.3099. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES