Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Jul;82(1):316–321. doi: 10.1172/JCI113589

Expression of novel interleukin 2 binding molecules and their functional roles in human B cell differentiation.

T Tanaka 1, O Saiki 1, S Doi 1, M Suemura 1, S Negoro 1, S Kishimoto 1
PMCID: PMC303511  PMID: 2839549

Abstract

Expressions and functional roles of novel IL-2 binding molecules (p70, 75) in the differentiation of B cells into Ig secreting cells were explored by using human several B cell lines and tonsillar B cells. Affinity-crosslinking studies revealed that five of nine B cell lines expressed p70 and p75 without detectable Tac antigen (p55) expression and the expression was associated with B cell maturation. In tonsillar B cells, small high-density B cells did not express p70 and p75, whereas large low-density B cells, which were thought to be activated in vivo, expressed them. Binding assays of radiolabeled IL-2 showed that the affinity of these molecules was intermediate (kD = 1-3 nM, 700-3,000 sites/cell). Furthermore, high concentrations of IL-2 (greater than 100 U/ml) induced Ig productions in large B cells and two of five cell lines. These results taken together suggest that B cells may express novel IL-2 binding molecules, associated with B cell differentiation and differentiate into Ig secreting cells by IL-2 through novel IL-2 binding molecules.

Full text

PDF
319

Images in this article

Selected References

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

  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. Bich-Thuy L. T., Lane H. C., Fauci A. S. Recombinant interleukin-2-induced polyclonal proliferation of in vitro unstimulated human peripheral blood lymphocytes. Cell Immunol. 1986 Apr 1;98(2):396–410. doi: 10.1016/0008-8749(86)90299-6. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Farrar W. L., Anderson W. B. Interleukin-2 stimulates association of protein kinase C with plasma membrane. Nature. 1985 May 16;315(6016):233–235. doi: 10.1038/315233a0. [DOI] [PubMed] [Google Scholar]
  5. Fujii M., Sugamura K., Sano K., Nakai M., Sugita K., Hinuma Y. High-affinity receptor-mediated internalization and degradation of interleukin 2 in human T cells. J Exp Med. 1986 Mar 1;163(3):550–562. doi: 10.1084/jem.163.3.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  7. Goldsmith P. K. A highly sensitive enzyme-linked immunosorbent assay for human immunoglobulin E: comparison of microtiter plate and disk methodologies. Anal Biochem. 1981 Oct;117(1):53–60. doi: 10.1016/0003-2697(81)90690-4. [DOI] [PubMed] [Google Scholar]
  8. Henney C. S., Kuribayashi K., Kern D. E., Gillis S. Interleukin-2 augments natural killer cell activity. Nature. 1981 May 28;291(5813):335–338. doi: 10.1038/291335a0. [DOI] [PubMed] [Google Scholar]
  9. Lê thi Bich-Thuy, Fauci A. S. Direct effect of interleukin 2 on the differentiation of human B cells which have not been preactivated in vitro. Eur J Immunol. 1985 Nov;15(11):1075–1079. doi: 10.1002/eji.1830151102. [DOI] [PubMed] [Google Scholar]
  10. Mingari M. C., Gerosa F., Carra G., Accolla R. S., Moretta A., Zubler R. H., Waldmann T. A., Moretta L. Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells. Nature. 1984 Dec 13;312(5995):641–643. doi: 10.1038/312641a0. [DOI] [PubMed] [Google Scholar]
  11. Morgan D. A., Ruscetti F. W., Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007–1008. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
  12. Nakagawa T., Hirano T., Nakagawa N., Yoshizaki K., Kishimoto T. Effect of recombinant IL 2 and gamma-IFN on proliferation and differentiation of human B cells. J Immunol. 1985 Feb;134(2):959–966. [PubMed] [Google Scholar]
  13. Ralph P., Jeong G., Welte K., Mertelsmann R., Rabin H., Henderson L. E., Souza L. M., Boone T. C., Robb R. J. Stimulation of immunoglobulin secretion in human B lymphocytes as a direct effect of high concentrations of IL 2. J Immunol. 1984 Nov;133(5):2442–2445. [PubMed] [Google Scholar]
  14. Robb R. J., Greene W. C. Internalization of interleukin 2 is mediated by the beta chain of the high-affinity interleukin 2 receptor. J Exp Med. 1987 Apr 1;165(4):1201–1206. doi: 10.1084/jem.165.4.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Robb R. J., Rusk C. M., Yodoi J., Greene W. C. Interleukin 2 binding molecule distinct from the Tac protein: analysis of its role in formation of high-affinity receptors. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2002–2006. doi: 10.1073/pnas.84.7.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Romagnani S., Del Prete G., Giudizi M. G., Biagiotti R., Almerigogna F., Tiri A., Alessi A., Mazzetti M., Ricci M. Direct induction of human B-cell differentiation by recombinant interleukin-2. Immunology. 1986 May;58(1):31–35. [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Tanaka T., Saiki O., Doi S., Hatakeyama M., Doi T., Kono T., Mori H., Fujii M., Sugamura K., Negoro S. Functional interleukin 2 receptors on B cells lacking Tac antigens. Eur J Immunol. 1987 Sep;17(9):1379–1382. doi: 10.1002/eji.1830170925. [DOI] [PubMed] [Google Scholar]
  20. Tanaka T., Saiki O., Doi S., Negoro S., Kishimoto S. Interleukin 2 functions through novel interleukin 2 binding molecules in T cells. J Immunol. 1988 Jan 15;140(2):470–473. [PubMed] [Google Scholar]
  21. 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]
  22. Tsudo M., Goldman C. K., Bongiovanni K. F., Chan W. C., Winton E. F., Yagita M., Grimm E. A., Waldmann T. A. 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 U S A. 1987 Aug;84(15):5394–5398. doi: 10.1073/pnas.84.15.5394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Tsudo M., Uchiyama T., Uchino H. Expression of Tac antigen on activated normal human B cells. J Exp Med. 1984 Aug 1;160(2):612–617. doi: 10.1084/jem.160.2.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Waldmann T. A., Goldman C. K., Robb R. J., Depper J. M., Leonard W. J., Sharrow S. O., Bongiovanni K. F., Korsmeyer S. J., Greene W. C. Expression of interleukin 2 receptors on activated human B cells. J Exp Med. 1984 Nov 1;160(5):1450–1466. doi: 10.1084/jem.160.5.1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weyand C. M., Goronzy J., Dallman M. J., Fathman C. G. Administration of recombinant interleukin 2 in vivo induces a polyclonal IgM response. J Exp Med. 1986 Jun 1;163(6):1607–1612. doi: 10.1084/jem.163.6.1607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Weyand C., Goronzy J., Fathman C. G., O'Hanley P. Administration in vivo of recombinant interleukin 2 protects mice against septic death. J Clin Invest. 1987 Jun;79(6):1756–1763. doi: 10.1172/JCI113016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES