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. 1987 Apr;84(7):1799–1803. doi: 10.1073/pnas.84.7.1799

Continuing rearrangement of immunoglobulin and T-cell receptor genes in a Ha-ras-transformed lymphoid progenitor cell line.

A Alessandrini, J H Pierce, D Baltimore, S V Desiderio
PMCID: PMC304528  PMID: 3470759

Abstract

The arrangement of immunoglobulin genes has been examined in a series of lymphoid cell lines transformed with the Harvey murine sarcoma virus. One cell line, HAFTL-1, expresses antigenic markers characteristic of B-lymphoid cells and undergoes frequent rearrangement at the JH locus (where J = joining and H = heavy chain) during propagation in culture. By molecular cloning and nucleotide sequence determination, these rearrangements were found to represent the earliest postulated step in heavy chain gene assembly: the joining of a diversity (D) segment to a JH segment. The HAFTL-1 cell line also undergoes infrequent D beta-to-J beta joining at the T-cell receptor beta locus in culture. The observations presented here suggest that the HAFTL-1 cell line represents the early stage of B-cell differentiation at which immunoglobulin gene rearrangement is initiated.

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Selected References

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

  1. Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alt F. W., Enea V., Bothwell A. L., Baltimore D. Activity of multiple light chain genes in murine myeloma cells producing a single, functional light chain. Cell. 1980 Aug;21(1):1–12. doi: 10.1016/0092-8674(80)90109-9. [DOI] [PubMed] [Google Scholar]
  3. Alt F. W., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Alt F., Rosenberg N., Lewis S., Thomas E., Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell. 1981 Dec;27(2 Pt 1):381–390. doi: 10.1016/0092-8674(81)90421-9. [DOI] [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. Bernard O., Gough N. M. Nucleotide sequence of immunoglobulin heavy chain joining segments between translocated VH and mu constant regions genes. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3630–3634. doi: 10.1073/pnas.77.6.3630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Caccia N., Kronenberg M., Saxe D., Haars R., Bruns G. A., Goverman J., Malissen M., Willard H., Yoshikai Y., Simon M. The T cell receptor beta chain genes are located on chromosome 6 in mice and chromosome 7 in humans. Cell. 1984 Jul;37(3):1091–1099. doi: 10.1016/0092-8674(84)90443-4. [DOI] [PubMed] [Google Scholar]
  8. Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
  9. Cory S., Adams J. M., Kemp D. J. Somatic rearrangements forming active immunoglobulin mu genes in B and T lymphoid cell lines. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4943–4947. doi: 10.1073/pnas.77.8.4943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Desiderio S. V., Yancopoulos G. D., Paskind M., Thomas E., Boss M. A., Landau N., Alt F. W., Baltimore D. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature. 1984 Oct 25;311(5988):752–755. doi: 10.1038/311752a0. [DOI] [PubMed] [Google Scholar]
  11. Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. Gough N. M., Bernard O. Sequences of the joining region genes for immunoglobulin heavy chains and their role in generation of antibody diversity. Proc Natl Acad Sci U S A. 1981 Jan;78(1):509–513. doi: 10.1073/pnas.78.1.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Herr W., Perlmutter A. P., Gilbert W. Monoclonal AKR/J thymic leukemias contain multiple JH immunoglobulin gene rearrangements. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7433–7436. doi: 10.1073/pnas.80.24.7433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Holmes K. L., Pierce J. H., Davidson W. F., Morse H. C., 3rd Murine hematopoietic cells with pre-B or pre-B/myeloid characteristics are generated by in vitro transformation with retroviruses containing fes, ras, abl, and src oncogenes. J Exp Med. 1986 Aug 1;164(2):443–457. doi: 10.1084/jem.164.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kavaler J., Davis M. M., Chien Y. Localization of a T-cell receptor diversity-region element. Nature. 1984 Aug 2;310(5976):421–423. doi: 10.1038/310421a0. [DOI] [PubMed] [Google Scholar]
  17. Kurosawa Y., Tonegawa S. Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments. J Exp Med. 1982 Jan 1;155(1):201–218. doi: 10.1084/jem.155.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kurosawa Y., von Boehmer H., Haas W., Sakano H., Trauneker A., Tonegawa S. Identification of D segments of immunoglobulin heavy-chain genes and their rearrangement in T lymphocytes. Nature. 1981 Apr 16;290(5807):565–570. doi: 10.1038/290565a0. [DOI] [PubMed] [Google Scholar]
  19. Lewis S., Rosenberg N., Alt F., Baltimore D. Continuing kappa-gene rearrangement in a cell line transformed by Abelson murine leukemia virus. Cell. 1982 Oct;30(3):807–816. doi: 10.1016/0092-8674(82)90285-9. [DOI] [PubMed] [Google Scholar]
  20. Maki R., Kearney J., Paige C., Tonegawa S. Immunoglobulin gene rearrangement in immature B cells. Science. 1980 Sep 19;209(4463):1366–1369. doi: 10.1126/science.6774416. [DOI] [PubMed] [Google Scholar]
  21. Malissen M., Minard K., Mjolsness S., Kronenberg M., Goverman J., Hunkapiller T., Prystowsky M. B., Yoshikai Y., Fitch F., Mak T. W. Mouse T cell antigen receptor: structure and organization of constant and joining gene segments encoding the beta polypeptide. Cell. 1984 Jul;37(3):1101–1110. doi: 10.1016/0092-8674(84)90444-6. [DOI] [PubMed] [Google Scholar]
  22. Max E. E., Seidman J. G., Leder P. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3450–3454. doi: 10.1073/pnas.76.7.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  24. Pelicci P. G., Knowles D. M., 2nd, Dalla Favera R. Lymphoid tumors displaying rearrangements of both immunoglobulin and T cell receptor genes. J Exp Med. 1985 Sep 1;162(3):1015–1024. doi: 10.1084/jem.162.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perry R. P., Kelley D. E., Coleclough C., Kearney J. F. Organization and expression of immunoglobulin genes in fetal liver hybridomas. Proc Natl Acad Sci U S A. 1981 Jan;78(1):247–251. doi: 10.1073/pnas.78.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pierce J. H., Aaronson S. A. BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell. J Exp Med. 1982 Sep 1;156(3):873–887. doi: 10.1084/jem.156.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Rimm D. L., Horness D., Kucera J., Blattner F. R. Construction of coliphage lambda Charon vectors with BamHI cloning sites. Gene. 1980 Dec;12(3-4):301–309. doi: 10.1016/0378-1119(80)90113-4. [DOI] [PubMed] [Google Scholar]
  29. Rosenberg N., Baltimore D. A quantitative assay for transformation of bone marrow cells by Abelson murine leukemia virus. J Exp Med. 1976 Jun 1;143(6):1453–1463. doi: 10.1084/jem.143.6.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
  31. Sakano H., Kurosawa Y., Weigert M., Tonegawa S. Identification and nucleotide sequence of a diversity DNA segment (D) of immunoglobulin heavy-chain genes. Nature. 1981 Apr 16;290(5807):562–565. doi: 10.1038/290562a0. [DOI] [PubMed] [Google Scholar]
  32. Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. doi: 10.1038/286676a0. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Siden E. J., Baltimore D., Clark D., Rosenberg N. E. Immunoglobulin synthesis by lymphoid cells transformed in vitro by Abelson murine leukemia virus. Cell. 1979 Feb;16(2):389–396. doi: 10.1016/0092-8674(79)90014-x. [DOI] [PubMed] [Google Scholar]
  35. Siu G., Kronenberg M., Strauss E., Haars R., Mak T. W., Hood L. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor. 1984 Sep 27-Oct 3Nature. 311(5984):344–350. doi: 10.1038/311344a0. [DOI] [PubMed] [Google Scholar]
  36. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  37. Traunecker A., Kiefer M., Dembić Z., Steinmetz M., Karjalainen K. Rearrangements of T cell receptor loci can be found only rarely in B lymphoid cells. Eur J Immunol. 1986 Apr;16(4):430–434. doi: 10.1002/eji.1830160420. [DOI] [PubMed] [Google Scholar]
  38. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  39. Whitlock C. A., Ziegler S. F., Treiman L. J., Stafford J. I., Witte O. N. Differentiation of cloned populations of immature B cells after transformation with Abelson murine leukemia virus. Cell. 1983 Mar;32(3):903–911. doi: 10.1016/0092-8674(83)90075-2. [DOI] [PubMed] [Google Scholar]
  40. Yancopoulos G. D., Alt F. W. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell. 1985 Feb;40(2):271–281. doi: 10.1016/0092-8674(85)90141-2. [DOI] [PubMed] [Google Scholar]
  41. Yancopoulos G. D., Blackwell T. K., Suh H., Hood L., Alt F. W. Introduced T cell receptor variable region gene segments recombine in pre-B cells: evidence that B and T cells use a common recombinase. Cell. 1986 Jan 31;44(2):251–259. doi: 10.1016/0092-8674(86)90759-2. [DOI] [PubMed] [Google Scholar]
  42. Yancopoulos G. D., Desiderio S. V., Paskind M., Kearney J. F., Baltimore D., Alt F. W. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature. 1984 Oct 25;311(5988):727–733. doi: 10.1038/311727a0. [DOI] [PubMed] [Google Scholar]
  43. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
  44. Züiga M. C., D'Eustachio P., Ruddle N. H. Immunoglobulin heavy chain gene rearrangement and transcription in murine T cell hybrids and T lymphomas. Proc Natl Acad Sci U S A. 1982 May;79(9):3015–3019. doi: 10.1073/pnas.79.9.3015. [DOI] [PMC free article] [PubMed] [Google Scholar]

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