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. 1993 Jul 1;178(1):257–264. doi: 10.1084/jem.178.1.257

Inhibition of murine B and T lymphopoiesis in vivo by an anti- interleukin 7 monoclonal antibody

PMCID: PMC2191094  PMID: 8315381

Abstract

The effects of interleukin 7 (IL-7) on the growth and differentiation of murine B cell progenitors has been well characterized using in vitro culture methods. We have investigated the role of IL-7 in vivo using a monoclonal antibody that neutralizes IL-7. We find that treatment of mice with this antibody completely inhibits the development of B cell progenitors from the pro-B cell stage forward. We also provide evidence that all peripheral B cells, including those of the B-1 and conventional lineages, are derived from IL-7-dependent precursors. The results are consistent with the rapid turnover of B cell progenitors in the marrow, but a slow turnover of mature B cells in the periphery. In addition to effects on B cell development, anti-IL-7 treatment substantially reduced thymus cellularity, affecting all major thymic subpopulations.

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Selected References

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  1. Armitage R. J., Namen A. E., Sassenfeld H. M., Grabstein K. H. Regulation of human T cell proliferation by IL-7. J Immunol. 1990 Feb 1;144(3):938–941. [PubMed] [Google Scholar]
  2. Billips L. G., Petitte D., Dorshkind K., Narayanan R., Chiu C. P., Landreth K. S. Differential roles of stromal cells, interleukin-7, and kit-ligand in the regulation of B lymphopoiesis. Blood. 1992 Mar 1;79(5):1185–1192. [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Cooper M. D., Mulvaney D., Coutinho A., Cazenave P. A. A novel cell surface molecule on early B-lineage cells. Nature. 1986 Jun 5;321(6070):616–618. doi: 10.1038/321616a0. [DOI] [PubMed] [Google Scholar]
  6. Ehlich A., Schaal S., Gu H., Kitamura D., Müller W., Rajewsky K. Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development. Cell. 1993 Mar 12;72(5):695–704. doi: 10.1016/0092-8674(93)90398-a. [DOI] [PubMed] [Google Scholar]
  7. Finkelman F. D., Scher I., Mond J. J., Kessler S., Kung J. T., Metcalf E. S. Polyclonal activation of the murine immune system by an antibody to IgD. II. Generation of polyclonal antibody production and cells with surface IgG. J Immunol. 1982 Aug;129(2):638–646. [PubMed] [Google Scholar]
  8. Förster I., Rajewsky K. The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4781–4784. doi: 10.1073/pnas.87.12.4781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Hardy R. R., Hayakawa K. A developmental switch in B lymphopoiesis. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11550–11554. doi: 10.1073/pnas.88.24.11550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hayakawa K., Hardy R. R., Herzenberg L. A., Herzenberg L. A. Progenitors for Ly-1 B cells are distinct from progenitors for other B cells. J Exp Med. 1985 Jun 1;161(6):1554–1568. doi: 10.1084/jem.161.6.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hayakawa K., Hardy R. R., Herzenberg L. A. Peritoneal Ly-1 B cells: genetic control, autoantibody production, increased lambda light chain expression. Eur J Immunol. 1986 Apr;16(4):450–456. doi: 10.1002/eji.1830160423. [DOI] [PubMed] [Google Scholar]
  14. Hayakawa K., Hardy R. R., Stall A. M., Herzenberg L. A., Herzenberg L. A. Immunoglobulin-bearing B cells reconstitute and maintain the murine Ly-1 B cell lineage. Eur J Immunol. 1986 Oct;16(10):1313–1316. doi: 10.1002/eji.1830161021. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kantor A. B., Stall A. M., Adams S., Herzenberg L. A., Herzenberg L. A. Differential development of progenitor activity for three B-cell lineages. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3320–3324. doi: 10.1073/pnas.89.8.3320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Kitamura D., Kudo A., Schaal S., Müller W., Melchers F., Rajewsky K. A critical role of lambda 5 protein in B cell development. Cell. 1992 May 29;69(5):823–831. doi: 10.1016/0092-8674(92)90293-l. [DOI] [PubMed] [Google Scholar]
  19. Kitamura D., Rajewsky K. Targeted disruption of mu chain membrane exon causes loss of heavy-chain allelic exclusion. Nature. 1992 Mar 12;356(6365):154–156. doi: 10.1038/356154a0. [DOI] [PubMed] [Google Scholar]
  20. Landreth K. S., Narayanan R., Dorshkind K. Insulin-like growth factor-I regulates pro-B cell differentiation. Blood. 1992 Sep 1;80(5):1207–1212. [PubMed] [Google Scholar]
  21. 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]
  22. Morrissey P. J., Conlon P., Charrier K., Braddy S., Alpert A., Williams D., Namen A. E., Mochizuki D. Administration of IL-7 to normal mice stimulates B-lymphopoiesis and peripheral lymphadenopathy. J Immunol. 1991 Jul 15;147(2):561–568. [PubMed] [Google Scholar]
  23. 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]
  24. Mujumdar R. B., Ernst L. A., Mujumdar S. R., Waggoner A. S. Cyanine dye labeling reagents containing isothiocyanate groups. Cytometry. 1989 Jan;10(1):11–19. doi: 10.1002/cyto.990100104. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Nishimoto N., Kubagawa H., Ohno T., Gartland G. L., Stankovic A. K., Cooper M. D. Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6284–6288. doi: 10.1073/pnas.88.14.6284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Osmond D. G., Kim N., Manoukian R., Phillips R. A., Rico-Vargas S. A., Jacobsen K. Dynamics and localization of early B-lymphocyte precursor cells (pro-B cells) in the bone marrow of scid mice. Blood. 1992 Apr 1;79(7):1695–1703. [PubMed] [Google Scholar]
  28. Park L. S., Friend D. J., Schmierer A. E., Dower S. K., Namen A. E. Murine interleukin 7 (IL-7) receptor. Characterization on an IL-7-dependent cell line. J Exp Med. 1990 Apr 1;171(4):1073–1089. doi: 10.1084/jem.171.4.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Sato T. A., Widmer M. B., Finkelman F. D., Madani H., Jacobs C. A., Grabstein K. H., Maliszewski C. R. Recombinant soluble murine IL-4 receptor can inhibit or enhance IgE responses in vivo. J Immunol. 1993 Apr 1;150(7):2717–2723. [PubMed] [Google Scholar]
  32. Scher I., Titus J. A., Finkelman F. D. The ontogeny and distribution of B cells in normal and mutant immune-defective CBA/N mice: two-parameter analysis of surface IgM and IgD. J Immunol. 1983 Feb;130(2):619–625. [PubMed] [Google Scholar]
  33. 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]
  34. Snapper C. M., Finkelman F. D. Rapid loss of IgM expression by normal murine B cells undergoing IgG1 and IgE class switching after in vivo immunization. J Immunol. 1990 Dec 1;145(11):3654–3660. [PubMed] [Google Scholar]
  35. Sudo T., Ito M., Ogawa Y., Iizuka M., Kodama H., Kunisada T., Hayashi S., Ogawa M., Sakai K., Nishikawa S. Interleukin 7 production and function in stromal cell-dependent B cell development. J Exp Med. 1989 Jul 1;170(1):333–338. doi: 10.1084/jem.170.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vitetta E. S., Melcher U., McWilliams M., Lamm M. E., Phillips-Quagliata J. M., Uhr J. W. Cell surface immunoglobulin. XI. The appearance of an IgD-like molecule on murine lymphoid cells during ontogeny. J Exp Med. 1975 Jan 1;141(1):206–215. doi: 10.1084/jem.141.1.206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Williams D. E., Namen A. E., Mochizuki D. Y., Overell R. W. Clonal growth of murine pre-B colony-forming cells and their targeted infection by a retroviral vector: dependence on interleukin-7. Blood. 1990 Mar 1;75(5):1132–1138. [PubMed] [Google Scholar]
  38. Zitron I. M., Clevinger B. L. Regulation of murine B cells through surface immunoglobulin. I. Monoclonal anti-delta antibody that induces allotype-specific proliferation. J Exp Med. 1980 Nov 1;152(5):1135–1146. doi: 10.1084/jem.152.5.1135. [DOI] [PMC free article] [PubMed] [Google Scholar]

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