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. 1976 Feb 1;143(2):329–347. doi: 10.1084/jem.143.2.329

The adherence of human Fc receptor-bearing lymphocytes to antigen- antibody complexes. II. Morphologic alterations induced by the substrate

PMCID: PMC2190128  PMID: 814196

Abstract

The adhesion of human Fc receptor-bearing lymphocytes to immobilized antigen-antibody complexes is accompanied by marked alterations in cell shape, resulting in flattening of greater than 90% of the adherent cells. In addition, about 65% of the adherent cells become elongated, with distinct uropods being present in about 1/3 of these cells. Scanning electron microscopy demonstrates that most of the surface microvilli are lost, while ruffled membranes and long microextensions are formed during the shape change. Time-lapse cinematography shows that the major shape changes occur within a few minutes after contact with the substrate, and that the adherent cells undergo translational motility. Both flattening and elongation of the adherent cells are inhibited by low temperature, chelating agents, cytochalasin B, and vinblastine, while sodium azide selectively inhibits elongation and uropod formation. It is argued that these morphological changes result from an active response of the cell to the immobilized complexes, and that such alterations may be related mechanistically to the ability of the cells to kill antibody-coated target cells.

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Selected References

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  1. Abercrombie M., Heaysman J. E., Pegrum S. M. The locomotion of fibroblasts in culture. 3. Movements of particles on the dorsal surface of the leading lamella. Exp Cell Res. 1970 Oct;62(2):389–398. doi: 10.1016/0014-4827(70)90570-7. [DOI] [PubMed] [Google Scholar]
  2. Able M. E., Lee J. C., Rosenau W. Lymphocyte--target cell interaction in vitro. Ultrastructural and cinematographic studies. Am J Pathol. 1970 Sep;60(3):421–434. [PMC free article] [PubMed] [Google Scholar]
  3. Bensch K. G., Malawista S. E. Microtubular crystals in mammalian cells. J Cell Biol. 1969 Jan;40(1):95–107. doi: 10.1083/jcb.40.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Biberfeld P., Biberfeld G., Perlmann P., Holm G. Cytological observations on the cytotoxic interaction between lymphocytes and antibody-coated monolayer cells. Cell Immunol. 1973 Apr;7(1):60–72. doi: 10.1016/0008-8749(73)90182-2. [DOI] [PubMed] [Google Scholar]
  5. Biberfeld P., Biberfeld G., Perlmann P., Holm G. Cytological observations on the cytotoxic interaction between lymphocytes and antibody-coated monolayer cells. Cell Immunol. 1973 Apr;7(1):60–72. doi: 10.1016/0008-8749(73)90182-2. [DOI] [PubMed] [Google Scholar]
  6. Biberfeld P. Cytotoxic interaction of phytohemagglutinin-stimulated blood lymphocytes with monolayer cells: a study by light and electron microscopy. Cell Immunol. 1971 Feb;2(1):54–72. doi: 10.1016/0008-8749(71)90025-6. [DOI] [PubMed] [Google Scholar]
  7. Biberfeld P. Uropod formation in phytohaemagglutinin (PHA) stimulated lymphocytes. Exp Cell Res. 1971 Jun;66(2):433–445. doi: 10.1016/0014-4827(71)90698-7. [DOI] [PubMed] [Google Scholar]
  8. Cerottini J. C., Brunner K. T. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv Immunol. 1974;18:67–132. doi: 10.1016/s0065-2776(08)60308-9. [DOI] [PubMed] [Google Scholar]
  9. Chess L., MacDermott R. P., Schlossman S. F. Immunologic functions of isolated human lymphocyte subpopulations. I. Quantitative isolation of human T and B cells and response to mitogens. J Immunol. 1974 Oct;113(4):1113–1121. [PubMed] [Google Scholar]
  10. Choi T. K., Sleight D. R., Nisonoff A. General method for isolation and recovery of B cells bearing specific receptors. J Exp Med. 1974 Mar 1;139(3):761–766. doi: 10.1084/jem.139.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cohen H. J. Human lymphocyte surface immunoglobulin capping. Normal characteristics and anomalous behavior of chronic lymphocytic leukemic lymphocytes. J Clin Invest. 1975 Jan;55(1):84–93. doi: 10.1172/JCI107921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hawkins D. Biopolymer membrane: a model system for the study of the neutrophilic leukocyte response to immune complexes. J Immunol. 1971 Aug;107(2):344–352. [PubMed] [Google Scholar]
  13. Henkart P., Blumenthal R. Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2789–2793. doi: 10.1073/pnas.72.7.2789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Henney C. S., Bubbers J. E. Antigen-T lymphocyte interactions: inhibition by cytochalasin B. J Immunol. 1973 Jul;111(1):85–90. [PubMed] [Google Scholar]
  15. Henson P. M. The immunologic release of constituents from neutrophil leukocytes. I. The role of antibody and complement on nonphagocytosable surfaces or phagocytosable particles. J Immunol. 1971 Dec;107(6):1535–1546. [PubMed] [Google Scholar]
  16. LeVine D., Kaplan M. J., Greenaway P. J. The purification and characterization of wheat-germ agglutinin. Biochem J. 1972 Oct;129(4):847–856. doi: 10.1042/bj1290847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lewis W. H., Webster L. T. MIGRATION OF LYMPHOCYTES IN PLASMA CULTURES OF HUMAN LYMPH NODES. J Exp Med. 1921 Jan 31;33(2):261–269. doi: 10.1084/jem.33.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lipsky P. E., Rosenthal A. S. Macrophage-lymphocyte interaction. I. Characteristics of the antigen-independent-binding of guinea pig thymocytes and lymphocytes to syngeneic macrophages. J Exp Med. 1973 Oct 1;138(4):900–924. doi: 10.1084/jem.138.4.900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lipsky P. E., Rosenthal A. S. Macrophage-lymphocyte interaction. II. Antigen-mediated physical interactions between immune guinea pig lymph node lymphocytes and syngeneic macrophages. J Exp Med. 1975 Jan 1;141(1):138–154. doi: 10.1084/jem.141.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Martz E. Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. I. Resolution and characterization. J Immunol. 1975 Jul;115(1):261–267. [PubMed] [Google Scholar]
  21. McFarland W., Heilman D. H., Moorhead J. F. Functional anatomy of the lymphocyte in immunological reactions in vitro. J Exp Med. 1966 Nov 1;124(5):851–858. doi: 10.1084/jem.124.5.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McFarland W., Schechter G. P. The lymphocyte in immunological reactions in vitro: ultrastructural studies. Blood. 1970 May;35(5):683–688. [PubMed] [Google Scholar]
  23. Mosier D. E. A requirement for two cell types for antibody formation in vitro. Science. 1967 Dec 22;158(3808):1573–1575. doi: 10.1126/science.158.3808.1573. [DOI] [PubMed] [Google Scholar]
  24. Nicolson G. L., Blaustein J. The interaction of Ricinus communis agglutinin with normal and tumor cell surfaces. Biochim Biophys Acta. 1972 May 9;266(2):543–547. doi: 10.1016/0005-2736(72)90109-5. [DOI] [PubMed] [Google Scholar]
  25. North R. J. The uptake of particulate antigens. J Reticuloendothel Soc. 1968 Jun;5(3):203–229. [PubMed] [Google Scholar]
  26. Olmsted J. B., Borisy G. G. Microtubules. Annu Rev Biochem. 1973;42:507–540. doi: 10.1146/annurev.bi.42.070173.002451. [DOI] [PubMed] [Google Scholar]
  27. Perlmann P., Holm G. Cytotoxic effects of lymphoid cells in vitro. Adv Immunol. 1969;11:117–193. doi: 10.1016/s0065-2776(08)60479-4. [DOI] [PubMed] [Google Scholar]
  28. Rabinovitch M., DeStefano M. J. Macrophage spreading in vitro. I. Inducers of spreading. Exp Cell Res. 1973 Mar 15;77(1):323–334. doi: 10.1016/0014-4827(73)90584-3. [DOI] [PubMed] [Google Scholar]
  29. Rabinovitch M., Destefano M. J. Macrophage spreading in vitro. II. Manganese and other metals as inducers or as co-factors for induced spreading. Exp Cell Res. 1973 Jun;79(2):423–430. doi: 10.1016/0014-4827(73)90462-x. [DOI] [PubMed] [Google Scholar]
  30. Rabinovitch M., Destefano M. J. Macrophage spreading in vitro. III. The effect of metabolic inhibitors, anesthetics and other drugs on spreading induced by subtilisin. Exp Cell Res. 1974 Sep;88(1):153–162. doi: 10.1016/0014-4827(74)90629-6. [DOI] [PubMed] [Google Scholar]
  31. Rajaraman R., Rounds D. E., Yen S. P., Rembaum A. A scanning electron microscope study of cell adhesion and spreading in vitro. Exp Cell Res. 1974 Oct;88(2):327–339. doi: 10.1016/0014-4827(74)90248-1. [DOI] [PubMed] [Google Scholar]
  32. Rosenstreich D. L., Shevach E., Green I., Rosenthal A. S. The uropod-bearing lymphocyte of the guinea pig. Evidence for thymic origin. J Exp Med. 1972 May 1;135(5):1037–1048. doi: 10.1084/jem.135.5.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rutishauser U., Yahara I., Edelman G. M. Morphology, motility, and surface behavior of lymphocytes bound to nylon fibers. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1149–1153. doi: 10.1073/pnas.71.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Unanue E. R., Ault K. A., Karnovsky M. J. Ligand-induced movement of lymphocyte surface macromolecules. IV. Stimulation of cell motility by anti-Ig and lack of relationship to capping. J Exp Med. 1974 Feb 1;139(2):295–312. doi: 10.1084/jem.139.2.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Unanue E. R. The regulatory role of macrophages in antigenic stimulation. Adv Immunol. 1972;15:95–165. doi: 10.1016/s0065-2776(08)60684-7. [DOI] [PubMed] [Google Scholar]
  36. Vasiliev J. M., Gelfand I. M., Domnina L. V., Ivanova O. Y., Komm S. G., Olshevskaja L. V. Effect of colcemid on the locomotory behaviour of fibroblasts. J Embryol Exp Morphol. 1970 Nov;24(3):625–640. [PubMed] [Google Scholar]
  37. Werdelin O., Braendstrup O., Pedersen E. Macrophage-lymphocyte clusters in the immune response to soluble protein antigen in vitro. J Exp Med. 1974 Nov 1;140(5):1245–1259. doi: 10.1084/jem.140.5.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wessells N. K., Spooner B. S., Ash J. F., Bradley M. O., Luduena M. A., Taylor E. L., Wrenn J. T., Yamada K. Microfilaments in cellular and developmental processes. Science. 1971 Jan 15;171(3967):135–143. doi: 10.1126/science.171.3967.135. [DOI] [PubMed] [Google Scholar]
  39. Wilson L., Bamburg J. R., Mizel S. B., Grisham L. M., Creswell K. M. Interaction of drugs with microtubule proteins. Fed Proc. 1974 Feb;33(2):158–166. [PubMed] [Google Scholar]

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