Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Oct 1;90(19):9125–9129. doi: 10.1073/pnas.90.19.9125

Expression and function of the interleukin 7 receptor in murine lymphocytes.

T Sudo 1, S Nishikawa 1, N Ohno 1, N Akiyama 1, M Tamakoshi 1, H Yoshida 1, S Nishikawa 1
PMCID: PMC47514  PMID: 8415665

Abstract

A monoclonal antibody, A7R34, that recognizes the high-affinity interleukin 7 receptor (IL-7Ra) and blocks the binding between IL-7 and IL-7Ra has been produced. Cell surface staining with A7R34 demonstrated that IL-7Ra is expressed in both B- and T-cell lineages. In the bone marrow, immature B-lineage cells that do not express surface IgM were IL-7Ra+. In the thymus, IL-7Ra was detected in CD4-8- T cells and also in CD4 or CD8 single-positive cells but not in CD4+8+ double-positive cells. In the peripheral lymphoid tissues, both CD4 and CD8 single-positive cells were the major cell types that express IL-7Ra. Addition of A7R34 to a long-term B-precursor-cell culture inhibited proliferation of the B-lineage cells, indicating that IL-7 is an absolute requirement for in vitro B-cell genesis. Consistent with this in vitro result, continuous injection of A7R34 into an adult mouse resulted in a decrease of B-precursor cells and also of thymocytes, whereas a considerable fraction of mature B and T cells in the peripheral tissues persisted over 2 weeks of the experiment. When A7R34 injection is started from day 14 of gestation, it is possible to produce mice that lack B cells. These results indicate that IL-7 is an essential molecule for generation of both B and T cells in murine bone marrow and thymus, respectively. Moreover, IL-7Ra would be the sole receptor system regulating these processes.

Full text

PDF
9125

Images in this article

Selected References

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

  1. Armitage R. J., Ziegler S. F., Friend D. J., Park L. S., Fanslow W. C. Identification of a novel low-affinity receptor for human interleukin-7. Blood. 1992 Apr 1;79(7):1738–1745. [PubMed] [Google Scholar]
  2. Aruffo A., Stamenkovic I., Melnick M., Underhill C. B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. doi: 10.1016/0092-8674(90)90694-a. [DOI] [PubMed] [Google Scholar]
  3. Chantry D., Turner M., Feldmann M. Interleukin 7 (murine pre-B cell growth factor/lymphopoietin 1) stimulates thymocyte growth: regulation by transforming growth factor beta. Eur J Immunol. 1989 Apr;19(4):783–786. doi: 10.1002/eji.1830190433. [DOI] [PubMed] [Google Scholar]
  4. Chazen G. D., Pereira G. M., LeGros G., Gillis S., Shevach E. M. Interleukin 7 is a T-cell growth factor. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5923–5927. doi: 10.1073/pnas.86.15.5923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coffman R. L. Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development. Immunol Rev. 1982;69:5–23. doi: 10.1111/j.1600-065x.1983.tb00446.x. [DOI] [PubMed] [Google Scholar]
  6. Collins L. S., Dorshkind K. A stromal cell line from myeloid long-term bone marrow cultures can support myelopoiesis and B lymphopoiesis. J Immunol. 1987 Feb 15;138(4):1082–1087. [PubMed] [Google Scholar]
  7. Conlon P. J., Morrissey P. J., Nordan R. P., Grabstein K. H., Prickett K. S., Reed S. G., Goodwin R., Cosman D., Namen A. E. Murine thymocytes proliferate in direct response to interleukin-7. Blood. 1989 Sep;74(4):1368–1373. [PubMed] [Google Scholar]
  8. Cumano A., Dorshkind K., Gillis S., Paige C. J. The influence of S17 stromal cells and interleukin 7 on B cell development. Eur J Immunol. 1990 Oct;20(10):2183–2189. doi: 10.1002/eji.1830201006. [DOI] [PubMed] [Google Scholar]
  9. Damia G., Komschlies K. L., Faltynek C. R., Ruscetti F. W., Wiltrout R. H. Administration of recombinant human interleukin-7 alters the frequency and number of myeloid progenitor cells in the bone marrow and spleen of mice. Blood. 1992 Mar 1;79(5):1121–1129. [PubMed] [Google Scholar]
  10. Faltynek C. R., Wang S., Miller D., Young E., Tiberio L., Kross K., Kelley M., Kloszewski E. Administration of human recombinant IL-7 to normal and irradiated mice increases the numbers of lymphocytes and some immature cells of the myeloid lineage. J Immunol. 1992 Aug 15;149(4):1276–1282. [PubMed] [Google Scholar]
  11. Goodwin R. G., Friend D., Ziegler S. F., Jerzy R., Falk B. A., Gimpel S., Cosman D., Dower S. K., March C. J., Namen A. E. Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. Cell. 1990 Mar 23;60(6):941–951. doi: 10.1016/0092-8674(90)90342-c. [DOI] [PubMed] [Google Scholar]
  12. Grabstein K. H., Namen A. E., Shanebeck K., Voice R. F., Reed S. G., Widmer M. B. Regulation of T cell proliferation by IL-7. J Immunol. 1990 Apr 15;144(8):3015–3020. [PubMed] [Google Scholar]
  13. Hardy R. R., Carmack C. E., Shinton S. A., Kemp J. D., Hayakawa K. Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J Exp Med. 1991 May 1;173(5):1213–1225. doi: 10.1084/jem.173.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hayashi S., Kunisada T., Ogawa M., Sudo T., Kodama H., Suda T., Nishikawa S., Nishikawa S. Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules. J Exp Med. 1990 May 1;171(5):1683–1695. doi: 10.1084/jem.171.5.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hirayama F., Shih J. P., Awgulewitsch A., Warr G. W., Clark S. C., Ogawa M. Clonal proliferation of murine lymphohemopoietic progenitors in culture. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5907–5911. doi: 10.1073/pnas.89.13.5907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hunt P., Robertson D., Weiss D., Rennick D., Lee F., Witte O. N. A single bone marrow-derived stromal cell type supports the in vitro growth of early lymphoid and myeloid cells. Cell. 1987 Mar 27;48(6):997–1007. doi: 10.1016/0092-8674(87)90708-2. [DOI] [PubMed] [Google Scholar]
  17. Ingalls H. M., Goodloe-Holland C. M., Luna E. J. Junctional plasma membrane domains isolated from aggregating Dictyostelium discoideum amebae. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4779–4783. doi: 10.1073/pnas.83.13.4779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kincade P. W., Lee G., Pietrangeli C. E., Hayashi S., Gimble J. M. Cells and molecules that regulate B lymphopoiesis in bone marrow. Annu Rev Immunol. 1989;7:111–143. doi: 10.1146/annurev.iy.07.040189.000551. [DOI] [PubMed] [Google Scholar]
  19. Lee G., Namen A. E., Gillis S., Ellingsworth L. R., Kincade P. W. Normal B cell precursors responsive to recombinant murine IL-7 and inhibition of IL-7 activity by transforming growth factor-beta. J Immunol. 1989 Jun 1;142(11):3875–3883. [PubMed] [Google Scholar]
  20. McNiece I. K., Langley K. E., Zsebo K. M. The role of recombinant stem cell factor in early B cell development. Synergistic interaction with IL-7. J Immunol. 1991 Jun 1;146(11):3785–3790. [PubMed] [Google Scholar]
  21. Morrissey P. J., Conlon P., Braddy S., Williams D. E., Namen A. E., Mochizuki D. Y. Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia accelerates lymphocyte repopulation. J Immunol. 1991 Mar 1;146(5):1547–1552. [PubMed] [Google Scholar]
  22. Morrissey P. J., Goodwin R. G., Nordan R. P., Anderson D., Grabstein K. H., Cosman D., Sims J., Lupton S., Acres B., Reed S. G. Recombinant interleukin 7, pre-B cell growth factor, has costimulatory activity on purified mature T cells. J Exp Med. 1989 Mar 1;169(3):707–716. doi: 10.1084/jem.169.3.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Murray R., Suda T., Wrighton N., Lee F., Zlotnik A. IL-7 is a growth and maintenance factor for mature and immature thymocyte subsets. Int Immunol. 1989;1(5):526–531. doi: 10.1093/intimm/1.5.526. [DOI] [PubMed] [Google Scholar]
  24. Namen A. E., Lupton S., Hjerrild K., Wignall J., Mochizuki D. Y., Schmierer A., Mosley B., March C. J., Urdal D., Gillis S. Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature. 1988 Jun 9;333(6173):571–573. doi: 10.1038/333571a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Nishikawa S., Ogawa M., Nishikawa S., Kunisada T., Kodama H. B lymphopoiesis on stromal cell clone: stromal cell clones acting on different stages of B cell differentiation. Eur J Immunol. 1988 Nov;18(11):1767–1771. doi: 10.1002/eji.1830181117. [DOI] [PubMed] [Google Scholar]
  27. Ogawa M., Matsuzaki Y., Nishikawa S., Hayashi S., Kunisada T., Sudo T., Kina T., Nakauchi H., Nishikawa S. Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med. 1991 Jul 1;174(1):63–71. doi: 10.1084/jem.174.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ogawa M., Nishikawa S., Ikuta K., Yamamura F., Naito M., Takahashi K., Nishikawa S. B cell ontogeny in murine embryo studied by a culture system with the monolayer of a stromal cell clone, ST2: B cell progenitor develops first in the embryonal body rather than in the yolk sac. EMBO J. 1988 May;7(5):1337–1343. doi: 10.1002/j.1460-2075.1988.tb02949.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Osmond D. G. B cell development in the bone marrow. Semin Immunol. 1990 May;2(3):173–180. [PubMed] [Google Scholar]
  30. Park L. S., Friend D., Gillis S., Urdal D. L. Characterization of the cell surface receptor for granulocyte-macrophage colony-stimulating factor. J Biol Chem. 1986 Mar 25;261(9):4177–4183. [PubMed] [Google Scholar]
  31. Rolink A., Melchers F. Molecular and cellular origins of B lymphocyte diversity. Cell. 1991 Sep 20;66(6):1081–1094. doi: 10.1016/0092-8674(91)90032-t. [DOI] [PubMed] [Google Scholar]
  32. Rolink A., Streb M., Nishikawa S., Melchers F. The c-kit-encoded tyrosine kinase regulates the proliferation of early pre-B cells. Eur J Immunol. 1991 Oct;21(10):2609–2612. doi: 10.1002/eji.1830211044. [DOI] [PubMed] [Google Scholar]
  33. Samaridis J., Casorati G., Traunecker A., Iglesias A., Gutierrez J. C., Müller U., Palacios R. Development of lymphocytes in interleukin 7-transgenic mice. Eur J Immunol. 1991 Feb;21(2):453–460. doi: 10.1002/eji.1830210230. [DOI] [PubMed] [Google Scholar]
  34. Scahill S. J., Devos R., Van der Heyden J., Fiers W. Expression and characterization of the product of a human immune interferon cDNA gene in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4654–4658. doi: 10.1073/pnas.80.15.4654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schatz D. G., Oettinger M. A., Schlissel M. S. V(D)J recombination: molecular biology and regulation. Annu Rev Immunol. 1992;10:359–383. doi: 10.1146/annurev.iy.10.040192.002043. [DOI] [PubMed] [Google Scholar]
  36. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  37. Suda T., Okada S., Suda J., Miura Y., Ito M., Sudo T., Hayashi S., Nishikawa S., Nakauchi H. A stimulatory effect of recombinant murine interleukin-7 (IL-7) on B-cell colony formation and an inhibitory effect of IL-1 alpha. Blood. 1989 Nov 1;74(6):1936–1941. [PubMed] [Google Scholar]
  38. Suda T., Zlotnik A. IL-7 maintains the T cell precursor potential of CD3-CD4-CD8- thymocytes. J Immunol. 1991 May 1;146(9):3068–3073. [PubMed] [Google Scholar]
  39. Urlaub G., Chasin L. A. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4216–4220. doi: 10.1073/pnas.77.7.4216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Whitlock C. A., Tidmarsh G. F., Muller-Sieburg C., Weissman I. L. Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule. Cell. 1987 Mar 27;48(6):1009–1021. doi: 10.1016/0092-8674(87)90709-4. [DOI] [PubMed] [Google Scholar]
  41. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES