Skip to main content
Log in

Demonstration of high-affinity interleukin-2 receptors on B-chronic lymphocytic leukemia cells: Functional and structural characterization

  • Original article
  • Published:
Blut Aims and scope Submit manuscript

Summary

Functional and structural characteristics of interleukin 2 (IL-2) receptors on B-cell chronic lymphocytic leukemia (B-CLL) cells were analyzed by a proliferation assay, IL-2 binding assay and cross-linking study. In the3H-thymidine incorporation assay, purified B-CLL cells from four out of sixteen cases, in which the percentage of Tac antigen (Tac Ag) positive cells in peripheral blood lymphocytes ranged from 0 to 48.8%, responded to IL-2 (100 U/ml) after both 3- and 6-day incubation. No relationship was found between the responsiveness to IL-2 and the percentage of Tac Ag positive cells. In the radiolabeled IL-2 binding assay, however, B-CLL cells from all seven cases examined, including three cases with mitogenic response to IL-2 and four cases without mitogenic response, were shown to have both high- and low-affinity receptors. The number of high- and low-affinity receptors per cell ranged from 29–186 and from 420 to 1,800, respectively. Furthermore, with the affinity cross-linking method p55 (Tac Ag) and p70/75 were found even in cases without mitogenic response in their B-CLL cells. In conclusion, the B-CLL cells so far examined possessed high-affinity IL-2 receptors consisting of p55 and p70/75; nevertheless, this was not sufficient to respond to the mitogenic signal of IL-2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Armitage RJ, Cawley JC (1986) Normal and certain leukemic B cells express IL-2 receptors without in vitro activation. Clin Exp Immunol 63: 298–302

    Google Scholar 

  2. Burton J, Kay NE, Wagner D, Nelson DL (1987) Spontaneous secretion of soluble Tac IL-2 receptors by malignant CLL B cells. Blood [suppl 1] 70: 252a (abstr)

  3. Dukovich M, Wano Y, Thuy Lt B, Katz P, Cullen BR, Kehrl JH, Green WC (1987) A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. Nature 327: 518–522

    Google Scholar 

  4. Gillis S, Smith KA (1977) Long term culture of tumourspecific cytotoxic T cells. Nature 268: 154–156

    Google Scholar 

  5. Karray S, Merle-Beral H, Vazquez A, Gerard JP, Debre P, Galanaud P (1987) Functional heterogeneity of B-CLL lymphocytes: Dissociated responsiveness to growth factors and distinct requirements for a first activation signal. Blood 70: 1105–1108

    Google Scholar 

  6. Lantz O, Grillot-Courvalin C, Schmitt C, Fermand JP, Brouet JC (1985) Interleukin 2 induced proliferation of leukemic human B cells. J Exp Med 161: 1225–1230

    Google Scholar 

  7. Lowenthal JW, Zublar RH, Nabholz M, Macdonald HR (1985) Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. Nature 315: 669–672

    Google Scholar 

  8. Malkovska V, Murphy J, Hudson L, Bevan D (1987) Direct effect of interleukin 2 on chronic lymphocytic leukaemia B cell functions and morphology. Clin Exp Immunol 68: 677–684

    Google Scholar 

  9. Morgan DA, Ruscetti FW, Gallo R (1976) Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193: 1007–1008

    Google Scholar 

  10. Muraguchi A, Kehrl JH, Longo DL, Volkman DJ, Smith KA, Fauci AF (1985) Interleukin 2 receptors on human B cells. J Exp Med 161: 181–197

    Google Scholar 

  11. Nakagawa T, Nakagawa N, Ambrus JL Jr, Fauci AS (1988) Differential effects of interleukin 2 vs B cell growth factor on human B cells. J Immunol 140: 465–469

    Google Scholar 

  12. Naruo K, Hinuma S, Kato K, Koyama M, Tada H, Tsukamoto K (1985) Comparison of the biological properties of purified natural and recombinant human interleukin-2. Biochem Biophys Res Commun 128: 257–264

    Google Scholar 

  13. Perri RT, Kay NE (1987) Malignant chronic lymphocytic leukemia B cells express interleukin 2 receptors but fail to respond to interleukin 2's proliferative signal. Leukemia 1: 127–130

    Google Scholar 

  14. Robb RJ, Munck A, Smith KA (1981) T-cell growth factor receptors: quantitation, specificity, and biological relevance. J Exp Med 154: 1455–1474

    Google Scholar 

  15. Robb RJ, Green WC, Rusk CM (1984) Low and high affinity cellular receptors for interleukin 2: implications for the level of Tac antigen. J Exp Med 160: 1126–1146

    Google Scholar 

  16. Robb RJ, Rusk CM, Yodoi J, Green WC (1987) Interleukin 2 binding molecule distinct from the Tac protein: Analysis of its role in formation of high-affinity receptors. Proc Natl Acad Sci USA 84: 2002–2006

    Google Scholar 

  17. Sharon MR, Klausner RD, Cullen BR, Chizzonite R, Leonard WJ (1986) Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science 234: 859–863

    Google Scholar 

  18. Sharon M, Siegel JP, Tosato G, Yodoi J, Gerrard TL, Leonald WJ (1988) The human interleukin 2 receptor chain (p70). J Exp Med 167: 1265–1270

    Google Scholar 

  19. Smith KA (1980) T-cell growth factor. Immunol Rev 51: 337–339

    Google Scholar 

  20. Tamaki T, Yonezawa R, Kanakura Y, Katagiri S, Mizutani H, Kitani T, Tarui S (1986) Mitogenic response of neoplastic B cells: Comparison of reactivity toStaphylococcus aureus Cowan I and anti-immunoglobulin antibodies. Clin Exp Immunol 64: 181–187

    Google Scholar 

  21. Tanaka T, Saiki O, Doi S, Hatakeyama M, Doi T, Kono T, Mori H, Fujii M, Sugamura K, Negoro S, Taniguchi T, Kishimoto S (1987) Functional interleukin 2 receptors on B cells lacking Tac antigens. Eur J Immunol 17: 1379–1382

    Google Scholar 

  22. Tanaka T, Saiki O, Doi S, Negoro S, Kishimoto S (1988) Interleukin 2 functions through novel interleukin 2 binding molecules in T cells. J Immunol 140: 470–473

    Google Scholar 

  23. Tesigawara K, Wang HM, Kato K, Smith KA (1987) Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med 165: 223–238

    Google Scholar 

  24. Touw I, Dorssers L, Lowenberg B (1987) The proliferative response of B cell chronic lymphocytic leukemia to interleukin 2: Functional characterization of the interleukin 2 membrane receptors. Blood 69: 1667–1673

    Google Scholar 

  25. Tsudo M, Uchiyama T, Uchino H (1984) Expression of Tac antigen on activated normal human B cells. J Exp Med 160: 612–617

    Google Scholar 

  26. Tsudo M, Kozak RW, Goldman CK, Waldmann TA (1986) Demonstration of a non-Tac peptide that binds interleukin-2: a potential participant in a multichain interleukin-2 complex. Proc Natl Acad Sci USA 83: 9694–9678

    Google Scholar 

  27. Tsudo M, Kozak RW, Goldman CK, Waldmann TA (1987) Contribution of a p75 interleukin 2 binding peptide to a high-affinity interleukin 2 receptor complex. Proc Natl Acad Sci USA 84: 4215–4218

    Google Scholar 

  28. Tsudo M, Goldman CK, Bongiovanni KF, Chan WC, Winton EF, Yagita M, Grimm EA, Waldomann (1987) The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. Proc Natl Acad Sci USA 84: 5394–5398

    Google Scholar 

  29. Vazquez A, Auffredou MT, Gerard JP, Delfraissy JF, Galanaud P (1987) Sequential effect of a high molecular weight B cell growth factor and of interleukin 2 on activated human B cells. J Immunol 139: 2344–2348

    Google Scholar 

  30. Waldman TA, Goldman CK, Robb RJ, Depper JM, Leonald WJ, Sharrow SO, Bongiovanni KF, Korsmeyer SJ, Greene WC (1984) Expression of interleukin 2 receptors on activated human B cells. J Exp Med 160: 1450–1466

    Google Scholar 

  31. Wang HM, Smith KA (1987) The interleukin 2 receptor. J Exp Med 166: 1055–1069

    Google Scholar 

  32. Zubler RH, Lowenthal JW, Erand F, Hashimoto N, Devos R, MacDonald HR (1984) Activated B cells express receptors for, and proliferate in response to, pure interleukin 2. J Exp Med 160: 1170–1183

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yagura, H., Tamaki, T., Furitsu, T. et al. Demonstration of high-affinity interleukin-2 receptors on B-chronic lymphocytic leukemia cells: Functional and structural characterization. Blut 60, 181–186 (1990). https://doi.org/10.1007/BF01720273

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01720273

Key words

Navigation