Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Jun;86(11):4235–4239. doi: 10.1073/pnas.86.11.4235

Cross-linking of interleukin 4 to surface molecules on murine T and B lymphocytes.

R Fernandez-Botran 1, J W Uhr 1, E S Vitetta 1
PMCID: PMC287425  PMID: 2786209

Abstract

Interleukin 4 (IL-4) is a T-cell derived lymphokine with multiple activities on a variety of cells. An intriguing feature of the different IL-4-mediated activities is their requirements for markedly different concentrations of IL-4 even on the same cell population. To gain some insight into the phenomenon, we have analyzed the structure of IL-4-binding proteins on T and B cells by cross-linking different concentrations of 125I-labeled IL-4 (125I-IL-4) to cells. Cross-linking of 125I-IL-4 at relatively low concentrations in the presence of the cross-linking agent 3,3'-dithiobis(propionic acid hydroxysuccinimide ester) resulted in the detection of the previously described 60- to 75-kDa protein. At higher 125I-IL-4 concentrations, however, an additional molecule of 105 kDa was observed. Cross-linking of 125I-IL-4 to both molecules was specific; it was inhibited by the presence of a 50-fold excess of either unlabeled IL-4 or monoclonal anti-IL-4 antibody. Furthermore, considerable size heterogeneity of the IL-4-binding proteins was evident in different cell populations. These results suggest that IL-4 receptors might have a more complex structure than originally reported and/or that high concentrations of IL-4 might induce interactions of the previously described IL-4 receptor (60-75 kDa) with a 105-kDa molecule. Hence, it is possible that IL-4 might generate a different signal at high concentrations through interaction of its receptor with another membrane molecule.

Full text

PDF
4235

Images in this article

4236Image
on p.4236
4236Image
on p.4236
4237Image
on p.4237
4237Image
on p.4237
4237Image
on p.4237

Selected References

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

  1. Boom W. H., Liano D., Abbas A. K. Heterogeneity of helper/inducer T lymphocytes. II. Effects of interleukin 4- and interleukin 2-producing T cell clones on resting B lymphocytes. J Exp Med. 1988 Apr 1;167(4):1350–1363. doi: 10.1084/jem.167.4.1350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brooks K., Yuan D., Uhr J. W., Krammer P. H., Vitetta E. S. Lymphokine-induced IgM secretion by clones of neoplastic B cells. Nature. 1983 Apr 28;302(5911):825–826. doi: 10.1038/302825a0. [DOI] [PubMed] [Google Scholar]
  3. Coffman R. L., Carty J. A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol. 1986 Feb 1;136(3):949–954. [PubMed] [Google Scholar]
  4. Coffman R. L., Ohara J., Bond M. W., Carty J., Zlotnik A., Paul W. E. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol. 1986 Jun 15;136(12):4538–4541. [PubMed] [Google Scholar]
  5. Fernandez-Botran R., Krammer P. H., Diamantstein T., Uhr J. W., Vitetta E. S. B cell-stimulatory factor 1 (BSF-1) promotes growth of helper T cell lines. J Exp Med. 1986 Aug 1;164(2):580–593. doi: 10.1084/jem.164.2.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fernandez-Botran R., Sanders V. M., Oliver K. G., Chen Y. W., Krammer P. H., Uhr J. W., Vitetta E. S. Interleukin 4 mediates autocrine growth of helper T cells after antigenic stimulation. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9689–9693. doi: 10.1073/pnas.83.24.9689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fernandez-Botran R., Sanders V. M., Vitetta E. S. Interactions between receptors for interleukin 2 and interleukin 4 on lines of helper T cells (HT-2) and B lymphoma cells (BCL1). J Exp Med. 1989 Feb 1;169(2):379–391. doi: 10.1084/jem.169.2.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Herrmann T., Diamantstein T. The mouse high affinity IL 2 receptor complex. I. Evidence for a third molecule, the putative gamma-chain, associated with the alpha- and/or beta-chain of the receptor. Immunobiology. 1987 Sep;175(3):145–158. doi: 10.1016/s0171-2985(87)80024-4. [DOI] [PubMed] [Google Scholar]
  9. Hudak S. A., Gollnick S. O., Conrad D. H., Kehry M. R. Murine B-cell stimulatory factor 1 (interleukin 4) increases expression of the Fc receptor for IgE on mouse B cells. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4606–4610. doi: 10.1073/pnas.84.13.4606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Isakson P. C., Puré E., Vitetta E. S., Krammer P. H. T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. J Exp Med. 1982 Mar 1;155(3):734–748. doi: 10.1084/jem.155.3.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Klein E., Klein G., Nadkarni J. S., Nadkarni J. J., Wigzell H., Clifford P. Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res. 1968 Jul;28(7):1300–1310. [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Layton J. E., Krammer P. H., Hamaoka T., Uhr J. W., Vitetta E. S. Small and large B cells respond differently to T cell-derived B cell growth and differentiation factors. J Mol Cell Immunol. 1985;2(3):155–167. [PubMed] [Google Scholar]
  14. Lebman D. A., Coffman R. L. Interleukin 4 causes isotype switching to IgE in T cell-stimulated clonal B cell cultures. J Exp Med. 1988 Sep 1;168(3):853–862. doi: 10.1084/jem.168.3.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lowenthal J. W., Castle B. E., Christiansen J., Schreurs J., Rennick D., Arai N., Hoy P., Takebe Y., Howard M. Expression of high affinity receptors for murine interleukin 4 (BSF-1) on hemopoietic and nonhemopoietic cells. J Immunol. 1988 Jan 15;140(2):456–464. [PubMed] [Google Scholar]
  16. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  17. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  18. Mosmann T. R., Yokota T., Kastelein R., Zurawski S. M., Arai N., Takebe Y. Species-specificity of T cell stimulating activities of IL 2 and BSF-1 (IL 4): comparison of normal and recombinant, mouse and human IL 2 and BSF-1 (IL 4). J Immunol. 1987 Mar 15;138(6):1813–1816. [PubMed] [Google Scholar]
  19. Nakajima K., Hirano T., Koyama K., Kishimoto T. Detection of receptors for murine B cell stimulatory factor 1 (BSF1): presence of functional receptors on CBA/N splenic B cells. J Immunol. 1987 Aug 1;139(3):774–779. [PubMed] [Google Scholar]
  20. Noelle R., Krammer P. H., Ohara J., Uhr J. W., Vitetta E. S. Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6149–6153. doi: 10.1073/pnas.81.19.6149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ohara J., Coligan J. E., Zoon K., Maloy W. L., Paul W. E. High-efficiency purification and chemical characterization of B cell stimulatory factor-1/interleukin 4. J Immunol. 1987 Aug 15;139(4):1127–1134. [PubMed] [Google Scholar]
  22. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  23. Ohara J., Paul W. E. Receptors for B-cell stimulatory factor-1 expressed on cells of haematopoietic lineage. Nature. 1987 Feb 5;325(6104):537–540. doi: 10.1038/325537a0. [DOI] [PubMed] [Google Scholar]
  24. Oliver K., Krammer P. H., Tucker P. W., Vitetta E. S. The effects of cytokines and adherent cells on the interleukin 4-mediated induction of Ia antigens on resting B cells. Cell Immunol. 1987 May;106(2):428–436. doi: 10.1016/0008-8749(87)90185-7. [DOI] [PubMed] [Google Scholar]
  25. Oliver K., Noelle R. J., Uhr J. W., Krammer P. H., Vitetta E. S. B-cell growth factor (B-cell growth factor I or B-cell-stimulating factor, provisional 1) is a differentiation factor for resting B cells and may not induce cell growth. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2465–2467. doi: 10.1073/pnas.82.8.2465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Park L. S., Friend D., Grabstein K., Urdal D. L. Characterization of the high-affinity cell-surface receptor for murine B-cell-stimulating factor 1. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1669–1673. doi: 10.1073/pnas.84.6.1669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Park L. S., Friend D., Sassenfeld H. M., Urdal D. L. Characterization of the human B cell stimulatory factor 1 receptor. J Exp Med. 1987 Aug 1;166(2):476–488. doi: 10.1084/jem.166.2.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Paul W. E. Interleukin 4/B cell stimulatory factor 1: one lymphokine, many functions. FASEB J. 1987 Dec;1(6):456–461. doi: 10.1096/fasebj.1.6.3315808. [DOI] [PubMed] [Google Scholar]
  29. Purkerson J. M., Newberg M., Wise G., Lynch K. R., Isakson P. C. Interleukin 5 and interleukin 2 cooperate with interleukin 4 to induce IgG1 secretion from anti-Ig-treated B cells. J Exp Med. 1988 Sep 1;168(3):1175–1180. doi: 10.1084/jem.168.3.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rabin E. M., Mond J. J., Ohara J., Paul W. E. Interferon-gamma inhibits the action of B cell stimulatory factor (BSF)-1 on resting B cells. J Immunol. 1986 Sep 1;137(5):1573–1576. [PubMed] [Google Scholar]
  31. Rabin E. M., Ohara J., Paul W. E. B-cell stimulatory factor 1 activates resting B cells. Proc Natl Acad Sci U S A. 1985 May;82(9):2935–2939. doi: 10.1073/pnas.82.9.2935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Reynolds D. S., Boom W. H., Abbas A. K. Inhibition of B lymphocyte activation by interferon-gamma. J Immunol. 1987 Aug 1;139(3):767–773. [PubMed] [Google Scholar]
  33. Roehm N. W., Leibson H. J., Zlotnik A., Kappler J., Marrack P., Cambier J. C. Interleukin-induced increase in Ia expression by normal mouse B cells. J Exp Med. 1984 Sep 1;160(3):679–694. doi: 10.1084/jem.160.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Saragovi H., Malek T. R. Direct identification of the murine IL-2 receptor p55-p75 heterodimer in the absence of IL-2. J Immunol. 1988 Jul 15;141(2):476–482. [PubMed] [Google Scholar]
  35. Saragovi H., Malek T. R. The murine interleukin 2 receptor. Irreversible cross-linking of radiolabeled interleukin 2 to high affinity interleukin 2 receptors reveals a noncovalently associated subunit. J Immunol. 1987 Sep 15;139(6):1918–1926. [PubMed] [Google Scholar]
  36. Severinson E., Naito T., Tokumoto H., Fukushima D., Hirano A., Hama K., Honjo T. Interleukin 4 (IgG1 induction factor): a multifunctional lymphokine acting also on T cells. Eur J Immunol. 1987 Jan;17(1):67–72. doi: 10.1002/eji.1830170112. [DOI] [PubMed] [Google Scholar]
  37. Sideras P., Bergstedt-Lindqvist S., MacDonald H. R., Severinson E. Secretion of IgG1 induction factor by T cell clones and hybridomas. Eur J Immunol. 1985 Jun;15(6):586–593. doi: 10.1002/eji.1830150611. [DOI] [PubMed] [Google Scholar]
  38. Snapper C. M., Finkelman F. D., Paul W. E. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J Exp Med. 1988 Jan 1;167(1):183–196. doi: 10.1084/jem.167.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Snapper C. M., Finkelman F. D., Paul W. E. Regulation of IgG1 and IgE production by interleukin 4. Immunol Rev. 1988 Feb;102:51–75. doi: 10.1111/j.1600-065x.1988.tb00741.x. [DOI] [PubMed] [Google Scholar]
  40. Stevens T. L., Bossie A., Sanders V. M., Fernandez-Botran R., Coffman R. L., Mosmann T. R., Vitetta E. S. Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature. 1988 Jul 21;334(6179):255–258. doi: 10.1038/334255a0. [DOI] [PubMed] [Google Scholar]
  41. Vitetta E. S., Ohara J., Myers C. D., Layton J. E., Krammer P. H., Paul W. E. Serological, biochemical, and functional identity of B cell-stimulatory factor 1 and B cell differentiation factor for IgG1. J Exp Med. 1985 Nov 1;162(5):1726–1731. doi: 10.1084/jem.162.5.1726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Watson J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J Exp Med. 1979 Dec 1;150(6):1510–1519. doi: 10.1084/jem.150.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES