Abstract
We have assessed the state of rearrangement and expression of B- and T-cell antigen receptor genes in cells of Abelson murine leukemia virus-transformed thymomas and other tumors. We found that unrearranged TcR gamma genes are expressed, as are unrearranged C mu genes, in pre-T, pre-B, and myeloid cells. We also found TcR gamma genes rearranged and expressed in putative pre-T cells and in cells apparently committed to the B-cell lineage. This is in contrast to the data from more mature T- and B-cell tumors. We conclude that in immature lymphoid cells both immunoglobulin and TcR gamma genes are accessible for rearrangement. We discuss the implications of these observations for an understanding of the B-T lymphoid differentiation event.
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- Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., Brinster R. L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
- Alt F. W., Rosenberg N., Casanova R. J., Thomas E., Baltimore D. Immunoglobulin heavy-chain expression and class switching in a murine leukaemia cell line. Nature. 1982 Mar 25;296(5855):325–331. doi: 10.1038/296325a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Bank I., DePinho R. A., Brenner M. B., Cassimeris J., Alt F. W., Chess L. A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes. Nature. 1986 Jul 10;322(6075):179–181. doi: 10.1038/322179a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
- Coleclough C. Chance, necessity and antibody gene dynamics. Nature. 1983 May 5;303(5912):23–26. doi: 10.1038/303023a0. [DOI] [PubMed] [Google Scholar]
- Cook W. D., Metcalf D., Nicola N. A., Burgess A. W., Walker F. Malignant transformation of a growth factor-dependent myeloid cell line by Abelson virus without evidence of an autocrine mechanism. Cell. 1985 Jul;41(3):677–683. doi: 10.1016/s0092-8674(85)80048-9. [DOI] [PubMed] [Google Scholar]
- Cook W. D. Rapid thymomas induced by Abelson murine leukemia virus. Proc Natl Acad Sci U S A. 1982 May;79(9):2917–2921. doi: 10.1073/pnas.79.9.2917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cook W. D. Thymocyte subsets transformed by Abelson murine leukemia virus. Mol Cell Biol. 1985 Feb;5(2):390–397. doi: 10.1128/mcb.5.2.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dick J. E., Magli M. C., Huszar D., Phillips R. A., Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 1985 Aug;42(1):71–79. doi: 10.1016/s0092-8674(85)80102-1. [DOI] [PubMed] [Google Scholar]
- Forster A., Hobart M., Hengartner H., Rabbitts T. H. An immunoglobulin heavy-chain gene is altered in two T-cell clones. Nature. 1980 Aug 28;286(5776):897–899. doi: 10.1038/286897a0. [DOI] [PubMed] [Google Scholar]
- Garman R. D., Doherty P. J., Raulet D. H. Diversity, rearrangement, and expression of murine T cell gamma genes. Cell. 1986 Jun 6;45(5):733–742. doi: 10.1016/0092-8674(86)90787-7. [DOI] [PubMed] [Google Scholar]
- Gonda T. J., Sheiness D. K., Bishop J. M. Transcripts from the cellular homologs of retroviral oncogenes: distribution among chicken tissues. Mol Cell Biol. 1982 Jun;2(6):617–624. doi: 10.1128/mcb.2.6.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haars R., Kronenberg M., Gallatin W. M., Weissman I. L., Owen F. L., Hood L. Rearrangement and expression of T cell antigen receptor and gamma genes during thymic development. J Exp Med. 1986 Jul 1;164(1):1–24. doi: 10.1084/jem.164.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayday A. C., Saito H., Gillies S. D., Kranz D. M., Tanigawa G., Eisen H. N., Tonegawa S. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell. 1985 Feb;40(2):259–269. doi: 10.1016/0092-8674(85)90140-0. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Cohen D. I., Nielsen E. A., Davis M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. doi: 10.1038/308149a0. [DOI] [PubMed] [Google Scholar]
- Heilig J. S., Glimcher L. H., Kranz D. M., Clayton L. K., Greenstein J. L., Saito H., Maxam A. M., Burakoff S. J., Eisen H. N., Tonegawa S. Expression of the T-cell-specific gamma gene is unnecessary in T cells recognizing class II MHC determinants. Nature. 1985 Sep 5;317(6032):68–70. doi: 10.1038/317068a0. [DOI] [PubMed] [Google Scholar]
- Iwamoto A., Rupp F., Ohashi P. S., Walker C. L., Pircher H., Joho R., Hengartner H., Mak T. W. T cell-specific gamma genes in C57BL/10 mice. Sequence and expression of new constant and variable region genes. J Exp Med. 1986 May 1;163(5):1203–1212. doi: 10.1084/jem.163.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kemp D. J., Harris A. W., Adams J. M. Transcripts of the immunoglobulin C mu gene vary in structure and splicing during lymphoid development. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7400–7404. doi: 10.1073/pnas.77.12.7400. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kemp D. J., Harris A. W., Cory S., Adams J. M. Expression of the immunoglobulin C mu gene in mouse T and B lymphoid and myeloid cell lines. Proc Natl Acad Sci U S A. 1980 May;77(5):2876–2880. doi: 10.1073/pnas.77.5.2876. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kranz D. M., Saito H., Heller M., Takagaki Y., Haas W., Eisen H. N., Tonegawa S. Limited diversity of the rearranged T-cell gamma gene. 1985 Feb 28-Mar 6Nature. 313(6005):752–755. doi: 10.1038/313752a0. [DOI] [PubMed] [Google Scholar]
- Kronenberg M., Davis M. M., Early P. W., Hood L. E., Watson J. D. Helper and killer T cells do not express B cell immunoglobulin joining and constant region gene segments. J Exp Med. 1980 Dec 1;152(6):1745–1761. doi: 10.1084/jem.152.6.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kronenberg M., Siu G., Hood L. E., Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol. 1986;4:529–591. doi: 10.1146/annurev.iy.04.040186.002525. [DOI] [PubMed] [Google Scholar]
- 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]
- Lieberman M., Declève A., Ricciardi-Castagnoli P., Boniver J., Finn O. J., Kaplan H. S. Establishment, characterization and virus expression of cell lines derived from radiation- and virus-induced lymphomas of C57BL/Ka mice. Int J Cancer. 1979 Aug;24(2):168–177. doi: 10.1002/ijc.2910240208. [DOI] [PubMed] [Google Scholar]
- Max E. E., Maizel J. V., Jr, Leder P. The nucleotide sequence of a 5.5-kilobase DNA segment containing the mouse kappa immunoglobulin J and C region genes. J Biol Chem. 1981 May 25;256(10):5116–5120. [PubMed] [Google Scholar]
- McKearn J. P., McCubrey J., Fagg B. Enrichment of hematopoietic precursor cells and cloning of multipotential B-lymphocyte precursors. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7414–7418. doi: 10.1073/pnas.82.21.7414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Metcalf D. Clonal extinction of myelomonocytic leukemic cells by serum from mice injected with endotoxin. Int J Cancer. 1980 Feb 15;25(2):225–233. doi: 10.1002/ijc.2910250210. [DOI] [PubMed] [Google Scholar]
- O'Connor N. T., Wainscoat J. S., Weatherall D. J., Gatter K. C., Feller A. C., Isaacson P., Jones D., Lennert K., Pallesen G., Ramsey A. Rearrangement of the T-cell-receptor beta-chain gene in the diagnosis of lymphoproliferative disorders. Lancet. 1985 Jun 8;1(8441):1295–1297. doi: 10.1016/s0140-6736(85)92791-6. [DOI] [PubMed] [Google Scholar]
- Palacios R., Steinmetz M. Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell. 1985 Jul;41(3):727–734. doi: 10.1016/s0092-8674(85)80053-2. [DOI] [PubMed] [Google Scholar]
- Premkumar E., Potter M., Singer P. A., Sklar M. D. Synthesis, surface deposition, and secretion of immunoglobulins by Abelson virus-transformed lymphosarcoma cell lines. Cell. 1975 Oct;6(2):149–159. doi: 10.1016/0092-8674(75)90005-7. [DOI] [PubMed] [Google Scholar]
- Ralph P., Moore M. A., Nilsson K. Lysozyme synthesis by established human and murine histiocytic lymphoma cell lines. J Exp Med. 1976 Jun 1;143(6):1528–1533. doi: 10.1084/jem.143.6.1528. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riley S. C., Brock E. J., Kuehl W. M. Induction of light chain expression in a pre-B cell line by fusion to myeloma cells. Nature. 1981 Feb 26;289(5800):804–806. doi: 10.1038/289804a0. [DOI] [PubMed] [Google Scholar]
- Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
- Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Yanagi Y., Chan A., Chin B., Minden M., Mak T. W. Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line. Proc Natl Acad Sci U S A. 1985 May;82(10):3430–3434. doi: 10.1073/pnas.82.10.3430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]