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. 1996 Dec;89(4):569–572. doi: 10.1046/j.1365-2567.1996.d01-770.x

The influence of IL-7 V(D)J recombination.

U Döbbeling 1
PMCID: PMC1456594  PMID: 9014823

Abstract

The influence of interleukin-7 (IL-7) on V(D)J recombination was investigated directly in the V(D)J recombination competent pre-B-cell line 38B9. The addition of IL-7 to the medium reduced the V(D)J recombination rate by 52-64%. This reduction was insensitive to the addition of cyclosporin A, indicating that the repression by IL-7 is not mediated by phosphatase 2B. The repression mechanism of IL-7 did not synergize with those of the protein kinase C activator 12-O-Tetradecanoylphorbol-13-acetate (TPA) and the intracellular Ca2+ mobilizer thapsigargin. The actin of IL-7 blocked by the addition of the protein kinase A stimulator caffeine and the synthetic glucocorticoid dexamethasone. IL-7 did not change the m-RNA levels of the V(D)J recombination activating genes RAG-1 and RAG-2, therefore IL-7 must exert its influence on V(D)J recombination either by post-transcriptional regulation of the RAG genes or by the regulation of other genes that are involved in V(D)J recombination. Although IL-7 may be necessary for the induction of and maintenance of V(D)J recombination during some stages of lymphocyte precursor development, it reduces the V(D)J recombination activity in pre-B cells.

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Selected References

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  1. Appasamy P. M., Kenniston T. W., Jr, Weng Y., Holt E. C., Kost J., Chambers W. H. Interleukin 7-induced expression of specific T cell receptor gamma variable region genes in murine fetal liver cultures. J Exp Med. 1993 Dec 1;178(6):2201–2206. doi: 10.1084/jem.178.6.2201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Auphan N., DiDonato J. A., Rosette C., Helmberg A., Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science. 1995 Oct 13;270(5234):286–290. doi: 10.1126/science.270.5234.286. [DOI] [PubMed] [Google Scholar]
  3. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen P. Signal integration at the level of protein kinases, protein phosphatases and their substrates. Trends Biochem Sci. 1992 Oct;17(10):408–413. doi: 10.1016/0968-0004(92)90010-7. [DOI] [PubMed] [Google Scholar]
  5. Goulding N. J., Guyre P. M. Glucocorticoids, lipocortins and the immune response. Curr Opin Immunol. 1993 Feb;5(1):108–113. doi: 10.1016/0952-7915(93)90089-b. [DOI] [PubMed] [Google Scholar]
  6. Hepler J. R., Earp H. S., Harden T. K. Long-term phorbol ester treatment down-regulates protein kinase C and sensitizes the phosphoinositide signaling pathway to hormone and growth factor stimulation. Evidence for a role of protein kinase C in agonist-induced desensitization. J Biol Chem. 1988 Jun 5;263(16):7610–7619. [PubMed] [Google Scholar]
  7. Hesse J. E., Lieber M. R., Gellert M., Mizuuchi K. Extrachromosomal DNA substrates in pre-B cells undergo inversion or deletion at immunoglobulin V-(D)-J joining signals. Cell. 1987 Jun 19;49(6):775–783. doi: 10.1016/0092-8674(87)90615-5. [DOI] [PubMed] [Google Scholar]
  8. Jonat C., Rahmsdorf H. J., Park K. K., Cato A. C., Gebel S., Ponta H., Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. doi: 10.1016/0092-8674(90)90395-u. [DOI] [PubMed] [Google Scholar]
  9. Kallenbach S., Goodhardt M., Rougeon F. A rapid test for V(D)J recombinase activity. Nucleic Acids Res. 1990 Nov 25;18(22):6730–6730. doi: 10.1093/nar/18.22.6730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lin W. C., Desiderio S. V(D)J recombination and the cell cycle. Immunol Today. 1995 Jun;16(6):279–289. doi: 10.1016/0167-5699(95)80182-0. [DOI] [PubMed] [Google Scholar]
  11. Menetski J. P., Gellert M. V(D)J recombination activity in lymphoid cell lines is increased by agents that elevate cAMP. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9324–9328. doi: 10.1073/pnas.87.23.9324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mombaerts P., Iacomini J., Johnson R. S., Herrup K., Tonegawa S., Papaioannou V. E. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992 Mar 6;68(5):869–877. doi: 10.1016/0092-8674(92)90030-g. [DOI] [PubMed] [Google Scholar]
  13. Muegge K., Vila M. P., Durum S. K. Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene. Science. 1993 Jul 2;261(5117):93–95. doi: 10.1126/science.7686307. [DOI] [PubMed] [Google Scholar]
  14. Namen A. E., Schmierer A. E., March C. J., Overell R. W., Park L. S., Urdal D. L., Mochizuki D. Y. B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors. J Exp Med. 1988 Mar 1;167(3):988–1002. doi: 10.1084/jem.167.3.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Oettinger M. A., Schatz D. G., Gorka C., Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990 Jun 22;248(4962):1517–1523. doi: 10.1126/science.2360047. [DOI] [PubMed] [Google Scholar]
  16. Rich B. E., Leder P. Transgenic expression of interleukin 7 restores T cell populations in nude mice. J Exp Med. 1995 Mar 1;181(3):1223–1228. doi: 10.1084/jem.181.3.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schatz D. G., Oettinger M. A., Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell. 1989 Dec 22;59(6):1035–1048. doi: 10.1016/0092-8674(89)90760-5. [DOI] [PubMed] [Google Scholar]
  18. Scheinman R. I., Cogswell P. C., Lofquist A. K., Baldwin A. S., Jr Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science. 1995 Oct 13;270(5234):283–286. doi: 10.1126/science.270.5234.283. [DOI] [PubMed] [Google Scholar]
  19. Schreiber S. L., Crabtree G. R. The mechanism of action of cyclosporin A and FK506. Immunol Today. 1992 Apr;13(4):136–142. doi: 10.1016/0167-5699(92)90111-J. [DOI] [PubMed] [Google Scholar]
  20. Schüle R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. doi: 10.1016/0092-8674(90)90397-w. [DOI] [PubMed] [Google Scholar]
  21. Shinkai Y., Rathbun G., Lam K. P., Oltz E. M., Stewart V., Mendelsohn M., Charron J., Datta M., Young F., Stall A. M. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992 Mar 6;68(5):855–867. doi: 10.1016/0092-8674(92)90029-c. [DOI] [PubMed] [Google Scholar]
  22. Whitlock C. A., Witte O. N. Long-term culture of B lymphocytes and their precursors from murine bone marrow. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3608–3612. doi: 10.1073/pnas.79.11.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wieland S., Döbbeling U., Rusconi S. Interference and synergism of glucocorticoid receptor and octamer factors. EMBO J. 1991 Sep;10(9):2513–2521. doi: 10.1002/j.1460-2075.1991.tb07791.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Winkler T. H., Melchers F., Rolink A. G. Interleukin-3 and interleukin-7 are alternative growth factors for the same B-cell precursors in the mouse. Blood. 1995 Apr 15;85(8):2045–2051. [PubMed] [Google Scholar]
  25. Yang-Yen H. F., Chambard J. C., Sun Y. L., Smeal T., Schmidt T. J., Drouin J., Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990 Sep 21;62(6):1205–1215. doi: 10.1016/0092-8674(90)90396-v. [DOI] [PubMed] [Google Scholar]
  26. Young S., Parker P. J., Ullrich A., Stabel S. Down-regulation of protein kinase C is due to an increased rate of degradation. Biochem J. 1987 Jun 15;244(3):775–779. doi: 10.1042/bj2440775. [DOI] [PMC free article] [PubMed] [Google Scholar]

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