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. 1994 Mar;81(3):381–388.

IFN-gamma abrogates IL-7-dependent proliferation in pre-B cells, coinciding with onset of apoptosis.

B A Garvy 1, R L Riley 1
PMCID: PMC1422354  PMID: 7515846

Abstract

These studies investigated the mechanism by which interferon-gamma (IFN-gamma) inhibits the interleukin-7 (IL-7)-dependent proliferation of BALB/c bone marrow B-cell precursors in vitro. Low concentrations (1 U/ml) of recombinant murine IFN-gamma (rmIFN-gamma) caused a approximately 80% suppression of IL-7 colony-forming units (CFU) formation in semi-solid media, in part through a direct affect on isolated B220+ pre-B cells. IFN-gamma did not induce apoptosis in small resting pre-B cells in BALB/c bone marrow. There was no difference in the proportion of apoptotic B220+ pre-B cells in IFN-gamma-treated cultures compared to cultures treated with IL-7 alone. However, IL-7-responsive pre-B cells generated from bone marrow had a 30-50% loss in cells in S+G2/M phases of the cell cycle and an increase of up to twice as many in apoptotic cells within 48 hr of exposure to IFN-gamma. Notably, expression of the tyrosine phosphatase B220 was increased in the IFN-gamma-treated pre-B cells. Interestingly, although there was no substantial change in IL-7 receptor mRNA expression upon IFN-gamma treatment, a small decrease in binding of biotinylated IL-7 to IFN-gamma-treated pre-B cells was observed. These results suggest that IFN-gamma inhibits IL-7 responsiveness in pre-B cells, resulting in a subtle down-regulation of IL-7 binding, inhibition of proliferation and, ultimately, apoptosis.

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Selected References

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  1. Buschle M., Campana D., Carding S. R., Richard C., Hoffbrand A. V., Brenner M. K. Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia. J Exp Med. 1993 Jan 1;177(1):213–218. doi: 10.1084/jem.177.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DePasquale-Jardieu P., Fraker P. J. Further characterization of the role of corticosterone in the loss of humoral immunity in zinc-deficient A/J mice as determined by adrenalectomy. J Immunol. 1980 Jun;124(6):2650–2655. [PubMed] [Google Scholar]
  3. Garvy B. A., Elia J. M., Hamilton B. L., Riley R. L. Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction. Blood. 1993 Nov 1;82(9):2758–2766. [PubMed] [Google Scholar]
  4. Garvy B. A., Telford W. G., King L. E., Fraker P. J. Glucocorticoids and irradiation-induced apoptosis in normal murine bone marrow B-lineage lymphocytes as determined by flow cytometry. Immunology. 1993 Jun;79(2):270–277. [PMC free article] [PubMed] [Google Scholar]
  5. Gimble J. M., Medina K., Hudson J., Robinson M., Kincade P. W. Modulation of lymphohematopoiesis in long-term cultures by gamma interferon: direct and indirect action on lymphoid and stromal cells. Exp Hematol. 1993 Feb;21(2):224–230. [PubMed] [Google Scholar]
  6. 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]
  7. Grawunder U., Melchers F., Rolink A. Interferon-gamma arrests proliferation and causes apoptosis in stromal cell/interleukin-7-dependent normal murine pre-B cell lines and clones in vitro, but does not induce differentiation to surface immunoglobulin-positive B cells. Eur J Immunol. 1993 Feb;23(2):544–551. doi: 10.1002/eji.1830230237. [DOI] [PubMed] [Google Scholar]
  8. Johnson P., Greenbaum L., Bottomly K., Trowbridge I. S. Identification of the alternatively spliced exons of murine CD45 (T200) required for reactivity with B220 and other T200-restricted antibodies. J Exp Med. 1989 Mar 1;169(3):1179–1184. doi: 10.1084/jem.169.3.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Koike K., Ma F., Shiohara M., Kubo T., Takagi M., Amano Y., Nakahata T., Komiyama A. Interferon-gamma inhibits proliferation, but not commitment, of murine granulocyte-macrophage progenitors. J Cell Physiol. 1992 Dec;153(3):528–533. doi: 10.1002/jcp.1041530313. [DOI] [PubMed] [Google Scholar]
  10. Kruger M. G., Riley R. L., Riley E. A., Elia J. M. Bone marrow stromal cells modulate both kappa light chain and Ly1 antigen expression on Ly1+ pre-B cell lines in vitro. Blood. 1990 Jul 15;76(2):383–392. [PubMed] [Google Scholar]
  11. 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]
  12. Ostergaard H. L., Trowbridge I. S. Negative regulation of CD45 protein tyrosine phosphatase activity by ionomycin in T cells. Science. 1991 Sep 20;253(5026):1423–1425. doi: 10.1126/science.1654595. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Pleiman C. M., Gimpel S. D., Park L. S., Harada H., Taniguchi T., Ziegler S. F. Organization of the murine and human interleukin-7 receptor genes: two mRNAs generated by differential splicing and presence of a type I-interferon-inducible promoter. Mol Cell Biol. 1991 Jun;11(6):3052–3059. doi: 10.1128/mcb.11.6.3052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rodriguez-Tarduchy G., Collins M., López-Rivas A. Regulation of apoptosis in interleukin-3-dependent hemopoietic cells by interleukin-3 and calcium ionophores. EMBO J. 1990 Sep;9(9):2997–3002. doi: 10.1002/j.1460-2075.1990.tb07492.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Roifman C. M., Wang G. X., Freedman M., Pan Z. Q. IL-7 receptor mediates tyrosine phosphorylation but does not activate the phosphatidylinositol-phospholipase C-gamma 1 pathway. J Immunol. 1992 Feb 15;148(4):1136–1142. [PubMed] [Google Scholar]
  17. Rolink A., Kudo A., Karasuyama H., Kikuchi Y., Melchers F. Long-term proliferating early pre B cell lines and clones with the potential to develop to surface Ig-positive, mitogen reactive B cells in vitro and in vivo. EMBO J. 1991 Feb;10(2):327–336. doi: 10.1002/j.1460-2075.1991.tb07953.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sherwood P. J., Weissman I. L. The growth factor IL-7 induces expression of a transformation-associated antigen in normal pre-B cells. Int Immunol. 1990;2(5):399–406. doi: 10.1093/intimm/2.5.399. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Telford W. G., King L. E., Fraker P. J. Evaluation of glucocorticoid-induced DNA fragmentation in mouse thymocytes by flow cytometry. Cell Prolif. 1991 Sep;24(5):447–459. doi: 10.1111/j.1365-2184.1991.tb01173.x. [DOI] [PubMed] [Google Scholar]
  21. Thomas M. L., Lefrançois L. Differential expression of the leucocyte-common antigen family. Immunol Today. 1988 Oct;9(10):320–326. doi: 10.1016/0167-5699(88)91326-6. [DOI] [PubMed] [Google Scholar]
  22. Thomas M. L. The leukocyte common antigen family. Annu Rev Immunol. 1989;7:339–369. doi: 10.1146/annurev.iy.07.040189.002011. [DOI] [PubMed] [Google Scholar]
  23. Uckun F. M., Dibirdik I., Smith R., Tuel-Ahlgren L., Chandan-Langlie M., Schieven G. L., Waddick K. G., Hanson M., Ledbetter J. A. Interleukin 7 receptor ligation stimulates tyrosine phosphorylation, inositol phospholipid turnover, and clonal proliferation of human B-cell precursors. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3589–3593. doi: 10.1073/pnas.88.9.3589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Volarević S., Niklinska B. B., Burns C. M., Yamada H., June C. H., Dumont F. J., Ashwell J. D. The CD45 tyrosine phosphatase regulates phosphotyrosine homeostasis and its loss reveals a novel pattern of late T cell receptor-induced Ca2+ oscillations. J Exp Med. 1992 Sep 1;176(3):835–844. doi: 10.1084/jem.176.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Welch P. A., Burrows P. D., Namen A., Gillis S., Cooper M. D. Bone marrow stromal cells and interleukin-7 induce coordinate expression of the BP-1/6C3 antigen and pre-B cell growth. Int Immunol. 1990;2(8):697–705. doi: 10.1093/intimm/2.8.697. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Xenocostas A., Lapp W. S., Osmond D. G. Suppression of B lymphocyte genesis in the bone marrow by systemic graft-versus-host reactions. Transplantation. 1987 Apr;43(4):549–555. doi: 10.1097/00007890-198704000-00019. [DOI] [PubMed] [Google Scholar]

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