Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1987 Jun 1;165(6):1565–1580. doi: 10.1084/jem.165.6.1565

The specific direct interaction of helper T cells and antigen- presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells

PMCID: PMC2188362  PMID: 2953845

Abstract

We have produced and investigated cell couples formed between cloned Th cells or T hybridoma cells, and either Ag-presenting B hybridoma or B lymphoma cells. The specific direct interaction between a Th and B-APC is here demonstrated by two rearrangements occurring inside the bound Th cell; the MTOC (and presumably the GA) is oriented to face the cell contact region with the B cell, and a membrane-associated cytoskeletal protein, talin, becomes concentrated under the contacting Th membrane. In the absence of the specific Ag or the correct Ia determinant, nonspecific T-B cell couples form that are morphologically indistinguishable from specific cell couples in the light microscope, but neither the MTOC nor the talin rearrangement occurs inside the bound T cell of such nonspecific couples. Furthermore, Ag processing by the B cell is required to produce the MTOC and talin rearrangements within the T cell in specific T-B couples. In the case of allogeneic Th- B cell couples, similar specific MTOC and talin rearrangements are observed inside the Th. Extracellular Ca2+ is required for the MTOC orientation to occur inside the specifically bound Th cell, but not for the talin rearrangement. It is proposed that the MTOC (and GA) reorientation and the talin rearrangement are involved in the directed secretion of GA-derived lymphokines from the Th cell to the bound B cell.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Bergmann J. E., Kupfer A., Singer S. J. Membrane insertion at the leading edge of motile fibroblasts. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1367–1371. doi: 10.1073/pnas.80.5.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berke G. Cytotoxic T-lymphocytes. How do they function? Immunol Rev. 1983;72:5–42. doi: 10.1111/j.1600-065x.1983.tb01071.x. [DOI] [PubMed] [Google Scholar]
  3. Burridge K., Connell L. A new protein of adhesion plaques and ruffling membranes. J Cell Biol. 1983 Aug;97(2):359–367. doi: 10.1083/jcb.97.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cline M. J., Swett V. C. The interaction of human monocytes and lymphocytes. J Exp Med. 1968 Dec 1;128(6):1309–1325. doi: 10.1084/jem.128.6.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hedrick S. M., Matis L. A., Hecht T. T., Samelson L. E., Longo D. L., Heber-Katz E., Schwartz R. H. The fine specificity of antigen and Ia determinant recognition by T cell hybridoma clones specific for pigeon cytochrome c. Cell. 1982 Aug;30(1):141–152. doi: 10.1016/0092-8674(82)90020-4. [DOI] [PubMed] [Google Scholar]
  6. Hersh E. M., Harris J. E. Macrophage-lymphocyte interaction in the antigen-induced blastogenic response of human peripheral blood leukocytes. J Immunol. 1968 Jun;100(6):1184–1194. [PubMed] [Google Scholar]
  7. Horwitz A., Duggan K., Buck C., Beckerle M. C., Burridge K. Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage. Nature. 1986 Apr 10;320(6062):531–533. doi: 10.1038/320531a0. [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. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kappler J., White J., Wegmann D., Mustain E., Marrack P. Antigen presentation by Ia+ B cell hybridomas to H-2-restricted T cell hybridomas. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3604–3607. doi: 10.1073/pnas.79.11.3604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kaye J., Porcelli S., Tite J., Jones B., Janeway C. A., Jr Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells. J Exp Med. 1983 Sep 1;158(3):836–856. doi: 10.1084/jem.158.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Knapp M. R., Severinson-Gronowicz E., Schröder J., Strober S. Characterization of a spontaneous murine B cell leukemia (BCL1). II. Tumor cell proliferation and IgM secretion after stimulation by LPS. J Immunol. 1979 Sep;123(3):1000–1006. [PubMed] [Google Scholar]
  13. Kupfer A., Dennert G. Reorientation of the microtubule-organizing center and the Golgi apparatus in cloned cytotoxic lymphocytes triggered by binding to lysable target cells. J Immunol. 1984 Nov;133(5):2762–2766. [PubMed] [Google Scholar]
  14. Kupfer A., Dennert G., Singer S. J. Polarization of the Golgi apparatus and the microtubule-organizing center within cloned natural killer cells bound to their targets. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7224–7228. doi: 10.1073/pnas.80.23.7224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kupfer A., Dennert G., Singer S. J. The reorientation of the Golgi apparatus and the microtubule-organizing center in the cytotoxic effector cell is a prerequisite in the lysis of bound target cells. J Mol Cell Immunol. 1985;2(1):37–49. [PubMed] [Google Scholar]
  16. Kupfer A., Louvard D., Singer S. J. Polarization of the Golgi apparatus and the microtubule-organizing center in cultured fibroblasts at the edge of an experimental wound. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2603–2607. doi: 10.1073/pnas.79.8.2603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kupfer A., Singer S. J., Dennert G. On the mechanism of unidirectional killing in mixtures of two cytotoxic T lymphocytes. Unidirectional polarization of cytoplasmic organelles and the membrane-associated cytoskeleton in the effector cell. J Exp Med. 1986 Mar 1;163(3):489–498. doi: 10.1084/jem.163.3.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kupfer A., Swain S. L., Janeway C. A., Jr, Singer S. J. The specific direct interaction of helper T cells and antigen-presenting B cells. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6080–6083. doi: 10.1073/pnas.83.16.6080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. LoCascio N. J., Haughton G., Arnold L. W., Corley R. B. Role of cell surface immunoglobulin in B-lymphocyte activation. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2466–2469. doi: 10.1073/pnas.81.8.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nemere I., Kupfer A., Singer S. J. Reorientation of the Golgi apparatus and the microtubule-organizing center inside macrophages subjected to a chemotactic gradient. Cell Motil. 1985;5(1):17–29. doi: 10.1002/cm.970050103. [DOI] [PubMed] [Google Scholar]
  21. Nowell J., Quaranta V. Chloroquine affects biosynthesis of Ia molecules by inhibiting dissociation of invariant (gamma) chains from alpha-beta dimers in B cells. J Exp Med. 1985 Oct 1;162(4):1371–1376. doi: 10.1084/jem.162.4.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Sanders V. M., Snyder J. M., Uhr J. W., Vitetta E. S. Characterization of the physical interaction between antigen-specific B and T cells. J Immunol. 1986 Oct 15;137(8):2395–2404. [PubMed] [Google Scholar]
  24. Shapiro D. N., Adams B. S., Niederhuber J. E. Antigen-specific T cell activation results in an increase in cytoplasmic free calcium. J Immunol. 1985 Oct;135(4):2256–2261. [PubMed] [Google Scholar]
  25. Sidman C. L., Marshall J. D., Shultz L. D., Gray P. W., Johnson H. M. Gamma-interferon is one of several direct B cell-maturing lymphokines. 1984 Jun 28-Jul 4Nature. 309(5971):801–804. doi: 10.1038/309801a0. [DOI] [PubMed] [Google Scholar]
  26. Singer S. J., Kupfer A. The directed migration of eukaryotic cells. Annu Rev Cell Biol. 1986;2:337–365. doi: 10.1146/annurev.cb.02.110186.002005. [DOI] [PubMed] [Google Scholar]
  27. Sredni B., Schwartz R. H. Antigen-specific, proliferating T lymphocyte clones. Methodology, specificity, MHC restriction and alloreactivity. Immunol Rev. 1981;54:187–223. doi: 10.1111/j.1600-065x.1981.tb00438.x. [DOI] [PubMed] [Google Scholar]
  28. Swain S. L., Dennert G., Warner J. F., Dutton R. W. Culture supernatants of a stimulated T-cell line have helper activity that acts synergistically with interleukin 2 in the response of B cells to antigen. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2517–2521. doi: 10.1073/pnas.78.4.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Swain S. L., Howard M., Kappler J., Marrack P., Watson J., Booth R., Wetzel G. D., Dutton R. W. Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays. J Exp Med. 1983 Sep 1;158(3):822–835. doi: 10.1084/jem.158.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Swain S. L. Role of BCGFII in the differentiation to antibody secretion normal and tumor B cells. J Immunol. 1985 Jun;134(6):3934–3943. [PubMed] [Google Scholar]
  31. Trelstad R. L. The Golgi apparatus in chick corneal epithelium: changes in intracellular position during development. J Cell Biol. 1970 Apr;45(1):34–42. doi: 10.1083/jcb.45.1.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ziegler H. K., Unanue E. R. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):175–178. doi: 10.1073/pnas.79.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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 The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES