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. 1992 Apr 15;89(8):3551–3555. doi: 10.1073/pnas.89.8.3551

Role and regulation of interleukin (IL)-2 receptor alpha and beta chains in IL-2-driven B-cell growth.

K Nakanishi 1, S Hirose 1, T Yoshimoto 1, H Ishizashi 1, K Hiroishi 1, T Tanaka 1, T Kono 1, M Miyasaka 1, T Taniguchi 1, K Higashino 1
PMCID: PMC48906  PMID: 1373502

Abstract

Substantial proportions of resting B cells constitutively express low levels of IL-2 receptor (IL-2R) alpha and/or beta chains. The expression of these chains is differentially regulated by anti-IgM and IL-2/IL-4. The anti-IgM induces IL-2R alpha chain expression, whereas each of the two cytokines induces IL-2R beta chain expression in a dose-dependent manner. Moreover, IL-2 induces the growth of B cells, when the cells were pretreated with IL-2 or IL-4 for 24 h. The magnitude of this IL-2-driven B-cell growth depends upon the level of IL-2R beta chain expression. Costimulation of the B cells with IL-2 and anti-IgM shifts the dose-response curve, and the cells proliferate at an IL-2 concentration as low as 40 pM. These results indicate that the levels of anti-IgM-induced IL-2R alpha chain and IL-2-induced IL-2R beta chain determine the sensitivity of the cells to IL-2.

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Selected References

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  1. Bich-Thuy L. T., Dukovich M., Peffer N. J., Fauci A. S., Kehrl J. H., Greene W. C. Direct activation of human resting T cells by IL 2: the role of an IL 2 receptor distinct from the Tac protein. J Immunol. 1987 Sep 1;139(5):1550–1556. [PubMed] [Google Scholar]
  2. Blackman M. A., Tigges M. A., Minie M. E., Koshland M. E. A model system for peptide hormone action in differentiation: interleukin 2 induces a B lymphoma to transcribe the J chain gene. Cell. 1986 Nov 21;47(4):609–617. doi: 10.1016/0092-8674(86)90625-2. [DOI] [PubMed] [Google Scholar]
  3. Caligiuri M. A., Zmuidzinas A., Manley T. J., Levine H., Smith K. A., Ritz J. Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors. J Exp Med. 1990 May 1;171(5):1509–1526. doi: 10.1084/jem.171.5.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dukovich M., Wano Y., Le thi Bich Thuy, Katz P., Cullen B. R., Kehrl J. H., Greene W. C. A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. Nature. 1987 Jun 11;327(6122):518–522. doi: 10.1038/327518a0. [DOI] [PubMed] [Google Scholar]
  5. Hatakeyama M., Doi T., Kono T., Maruyama M., Minamoto S., Mori H., Kobayashi M., Uchiyama T., Taniguchi T. Transmembrane signaling of interleukin 2 receptor. Conformation and function of human interleukin 2 receptor (p55)/insulin receptor chimeric molecules. J Exp Med. 1987 Aug 1;166(2):362–375. doi: 10.1084/jem.166.2.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hatakeyama M., Mori H., Doi T., Taniguchi T. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Cell. 1989 Dec 1;59(5):837–845. doi: 10.1016/0092-8674(89)90607-7. [DOI] [PubMed] [Google Scholar]
  7. Hatakeyama M., Tsudo M., Minamoto S., Kono T., Doi T., Miyata T., Miyasaka M., Taniguchi T. Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science. 1989 May 5;244(4904):551–556. doi: 10.1126/science.2785715. [DOI] [PubMed] [Google Scholar]
  8. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kondo S., Kinoshita M., Shimizu A., Saito Y., Konishi M., Sabe H., Honjo T. Expression and functional characterization of artificial mutants of interleukin-2 receptor. Nature. 1987 May 7;327(6117):64–67. doi: 10.1038/327064a0. [DOI] [PubMed] [Google Scholar]
  10. Kono T., Doi T., Yamada G., Hatakeyama M., Minamoto S., Tsudo M., Miyasaka M., Miyata T., Taniguchi T. Murine interleukin 2 receptor beta chain: dysregulated gene expression in lymphoma line EL-4 caused by a promoter insertion. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1806–1810. doi: 10.1073/pnas.87.5.1806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Leibson H. J., Marrack P., Kappler J. W. B cell helper factors. I. Requirement for both interleukin 2 and another 40,000 mol wt factor. J Exp Med. 1981 Nov 1;154(5):1681–1693. doi: 10.1084/jem.154.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Leonard W. J., Depper J. M., Crabtree G. R., Rudikoff S., Pumphrey J., Robb R. J., Krönke M., Svetlik P. B., Peffer N. J., Waldmann T. A. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):626–631. doi: 10.1038/311626a0. [DOI] [PubMed] [Google Scholar]
  13. Loughnan M. S., Nossal G. J. Interleukins 4 and 5 control expression of IL-2 receptor on murine B cells through independent induction of its two chains. Nature. 1989 Jul 6;340(6228):76–79. doi: 10.1038/340076a0. [DOI] [PubMed] [Google Scholar]
  14. Lowenthal J. W., Zubler R. H., Nabholz M., MacDonald H. R. Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. Nature. 1985 Jun 20;315(6021):669–672. doi: 10.1038/315669a0. [DOI] [PubMed] [Google Scholar]
  15. Malek T. R., Robb R. J., Shevach E. M. Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5694–5698. doi: 10.1073/pnas.80.18.5694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miller J., Malek T. R., Leonard W. J., Greene W. C., Shevach E. M., Germain R. N. Nucleotide sequence and expression of a mouse interleukin 2 receptor cDNA. J Immunol. 1985 Jun;134(6):4212–4217. [PubMed] [Google Scholar]
  17. Nakanishi K., Howard M., Muraguchi A., Farrar J., Takatsu K., Hamaoka T., Paul W. E. Soluble factors involved in B cell differentiation: identification of two distinct T cell-replacing factors (TRF). J Immunol. 1983 May;130(5):2219–2224. [PubMed] [Google Scholar]
  18. Nakanishi K., Malek T. R., Smith K. A., Hamaoka T., Shevach E. M., Paul W. E. Both interleukin 2 and a second T cell-derived factor in EL-4 supernatant have activity as differentiation factors in IgM synthesis. J Exp Med. 1984 Dec 1;160(6):1605–1621. doi: 10.1084/jem.160.6.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nakanishi K., Malek T. R., Smith K. A., Hamaoka T., Shevach E. M., Paul W. E. Both interleukin 2 and a second T cell-derived factor in EL-4 supernatant have activity as differentiation factors in IgM synthesis. J Exp Med. 1984 Dec 1;160(6):1605–1621. doi: 10.1084/jem.160.6.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakanishi K., Matsui K., Hirose S., Yoshimoto T., Hiroishi K., Kono T., Hada T., Hamaoka T., Higashino K. Lymphokine-regulated differential expression of mRNA for p75kDa-IL-2R and p55kDa-IL-2R in a cloned B lymphoma line (BLC1-CL-3 cells). J Immunol. 1990 Sep 1;145(5):1423–1429. [PubMed] [Google Scholar]
  21. Nikaido T., Shimizu A., Ishida N., Sabe H., Teshigawara K., Maeda M., Uchiyama T., Yodoi J., Honjo T. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):631–635. doi: 10.1038/311631a0. [DOI] [PubMed] [Google Scholar]
  22. Ohashi Y., Takeshita T., Nagata K., Mori S., Sugamura K. Differential expression of the IL-2 receptor subunits, p55 and p75 on various populations of primary peripheral blood mononuclear cells. J Immunol. 1989 Dec 1;143(11):3548–3555. [PubMed] [Google Scholar]
  23. Ortega G., Robb R. J., Shevach E. M., Malek T. R. The murine IL 2 receptor. I. Monoclonal antibodies that define distinct functional epitopes on activated T cells and react with activated B cells. J Immunol. 1984 Oct;133(4):1970–1975. [PubMed] [Google Scholar]
  24. Paul W. E., Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. doi: 10.1146/annurev.iy.05.040187.002241. [DOI] [PubMed] [Google Scholar]
  25. Robb R. J., Greene W. C., Rusk C. M. Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med. 1984 Oct 1;160(4):1126–1146. doi: 10.1084/jem.160.4.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sharon M., Klausner R. D., Cullen B. R., Chizzonite R., Leonard W. J. Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science. 1986 Nov 14;234(4778):859–863. doi: 10.1126/science.3095922. [DOI] [PubMed] [Google Scholar]
  27. Siegel J. P., Sharon M., Smith P. L., Leonard W. J. The IL-2 receptor beta chain (p70): role in mediating signals for LAK, NK, and proliferative activities. Science. 1987 Oct 2;238(4823):75–78. doi: 10.1126/science.3116668. [DOI] [PubMed] [Google Scholar]
  28. Smith K. A. Interleukin-2: inception, impact, and implications. Science. 1988 May 27;240(4856):1169–1176. doi: 10.1126/science.3131876. [DOI] [PubMed] [Google Scholar]
  29. Tanaka T., Tsudo M., Karasuyama H., Kitamura F., Kono T., Hatakeyama M., Taniguchi T., Miyasaka M. A novel monoclonal antibody against murine IL-2 receptor beta-chain. Characterization of receptor expression in normal lymphoid cells and EL-4 cells. J Immunol. 1991 Oct 1;147(7):2222–2228. [PubMed] [Google Scholar]
  30. Teshigawara K., Wang H. M., Kato K., Smith K. A. Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med. 1987 Jan 1;165(1):223–238. doi: 10.1084/jem.165.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tigges M. A., Casey L. S., Koshland M. E. Mechanism of interleukin-2 signaling: mediation of different outcomes by a single receptor and transduction pathway. Science. 1989 Feb 10;243(4892):781–786. doi: 10.1126/science.2492678. [DOI] [PubMed] [Google Scholar]
  32. Tsudo M., Kozak R. W., Goldman C. K., Waldmann T. A. Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694–9698. doi: 10.1073/pnas.83.24.9694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Waldmann T. A. The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science. 1986 May 9;232(4751):727–732. doi: 10.1126/science.3008337. [DOI] [PubMed] [Google Scholar]
  34. Yoshimoto T., Nakanishi K., Matsui K., Hirose S., Hiroishi K., Tanaka T., Hada T., Hamaoka T., Higashino K. IL-5 up-regulates but IL-4 down-regulates IL-2R expression on a cloned B lymphoma line. J Immunol. 1990 Jan 1;144(1):183–190. [PubMed] [Google Scholar]
  35. Zubler R. H., Lowenthal J. W., Erard F., Hashimoto N., Devos R., MacDonald H. R. Activated B cells express receptors for, and proliferate in response to, pure interleukin 2. J Exp Med. 1984 Oct 1;160(4):1170–1183. doi: 10.1084/jem.160.4.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]

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