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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Aug;56(2):331–338. doi: 10.1172/JCI108097

Membrane-bound immunoglobulins on human leukemic cells. Evidence for humoral immune responses of patients to leukemia-associated antigens.

R S Metzgar, T Mohanakumar, D S Miller
PMCID: PMC436591  PMID: 807598

Abstract

Immunoglobulins were detected on the membranes of human leukemic cells by a microcytotoxicity technique. A significant percentage of lymphocytes from normal donors failed to react with goat antisera to human heavy chain determinants or to lambda-light chains. Lymphocytes from some normal donors, however, did react with antisera to k-light chains. A high percentage (50-90) of cells from some leukemia patients were killed by antisera to light chains and by one or more antisera to heavy chain determinants. Trypsin treatment of leukemic cells resulted in a loss of cytotoxic activity with all immunoglobulin antisera. Reactivity with the k-light chain antiserum was detectable 2 h after trypsinization of chronic myeloid leukemic (CML) cells and 8 h after treatment of acute lymphocytic leukemic (ALL) cells. Reactivity with the antisera to heavy chain determinants and lambda-light chains could not be detected 8 and 48 h after trypsinization of CML and ALL cells, respectively. The cytotoxic activity of the immunoglobulin antisera to heavy chains was abolished by absorption with the specific immunoglobulin used to define the antisera by precipitation. Eluates (pH 3.2) prepared from leukemic cells which reacted by cytotoxicity with the immunoglobulin antisera were shown to contain immunoglobulins of different heavy chain classes. In addition, some of the eluates had cytotoxic antibody activity to human leukemia cells. The specificity of the eluted antibodies is similar to the specificity previously described for cytophilic antibodies from leukemic patients and nonhuman primate antisera to human leukemia cells. The possible in vitro detection and in vivo significance of the eluted non-complement-fixing antibodies is considered.

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Selected References

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  1. Abdou N. L., Abdou N. I. Immunoglobulin receptors on human leukocytes. IV. Differences between bone marrow and blood cells in multiple myeloma and chronic lymphocytic leukemia: effects of therapy. J Lab Clin Med. 1973 Oct;82(4):611–618. [PubMed] [Google Scholar]
  2. Aisenberg A. C., Bloch K. J. Immunoglobulins on the surface of neoplastic lymphocytes. N Engl J Med. 1972 Aug 10;287(6):272–276. doi: 10.1056/NEJM197208102870603. [DOI] [PubMed] [Google Scholar]
  3. Buckley R. H., Dees S. C., O'Fallon W. M. Serum immunoglobulins. I. Levels in normal children and in uncomplicated childhood allergy. Pediatrics. 1968 Mar;41(3):600–611. [PubMed] [Google Scholar]
  4. Eady R. P., Hough D. W., Kilshaw P. J., Stevenson G. T. Recovery of immunoglobulin removed from lymphocytic surfaces by proteolysis. Immunology. 1974 Mar;26(3):549–561. [PMC free article] [PubMed] [Google Scholar]
  5. Foulis A. K., Cochran A. J., Anderson J. R. Surface immunoglobulins of leukaemic cells. Clin Exp Immunol. 1973 Aug;14(4):481–490. [PMC free article] [PubMed] [Google Scholar]
  6. Fu S. M., Winchester R. J., Feizi T., Walzer P. D., Kunkel H. G. Idiotypic specificity of surface immunoglobulin and the maturation of leukemic bone-marrow-derived lymphocytes. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4487–4490. doi: 10.1073/pnas.71.11.4487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gleich G. J., Averbeck A. K., Swedlund H. A. Measurement of IgE in normal and allergic serum by radioimmunoassay. J Lab Clin Med. 1971 Apr;77(4):690–698. [PubMed] [Google Scholar]
  8. Gmelig Meyling F. H., Kooy-Blok L., Ballieux R. E. Complement-dependent cytolysis of human B lymphocytes with anti-light chain antisera. Eur J Immunol. 1974 May;4(5):332–337. doi: 10.1002/eji.1830040504. [DOI] [PubMed] [Google Scholar]
  9. Grey H. M., Rabellino E., Pirofsky B. Immunoglobulins on the surface of lymphocytes. IV. Distribution in hypogammaglobulinemia, cellular immune deficiency, and chronic lymphatic leukemia. J Clin Invest. 1971 Nov;50(11):2368–2375. doi: 10.1172/JCI106735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gutterman J. U., Rossen R. D., Butler W. T., McCredie K. B., Bodey G. P., Sr, Freireich E. J., Hersh E. M. Immunoglobulin on tumor cells and tumor-induced lymphocyte blastogenesis in human acute leukemia. N Engl J Med. 1973 Jan 25;288(4):169–175. doi: 10.1056/NEJM197301252880401. [DOI] [PubMed] [Google Scholar]
  11. Kinsky R., Voisin G. A., Hilgert I., Duc H. T. Biological properties of transplantation immune sera. II. PCA in mice with H-2 antigens. Transplantation. 1971 Sep;12(3):171–175. doi: 10.1097/00007890-197109000-00004. [DOI] [PubMed] [Google Scholar]
  12. Kubo R. T., Grey H. M., Pirofsky B. IgD: a major immunoglobulin on the surface of lymphocytes from patients with chronic lymphatic leukemia. J Immunol. 1974 May;112(5):1952–1954. [PubMed] [Google Scholar]
  13. Metzgar R. S., Mohanakumar T., Miller D. S. Antigens specific for human lymphocytic and myeloid leukemia cells: detection by nonhuman primate antiserums. Science. 1972 Dec 1;178(4064):986–988. doi: 10.1126/science.178.4064.986. [DOI] [PubMed] [Google Scholar]
  14. Mitchell M. S., Mokyr M. B., Aspnes G. T., McIntosh S. Cytophilic antibodies in man. Ann Intern Med. 1973 Sep;79(3):333–339. doi: 10.7326/0003-4819-79-3-333. [DOI] [PubMed] [Google Scholar]
  15. Mohanakumar T., Metzgar R. S., Miller D. S. Human leukemia cell antigens: serologic characterization with xenoantisera. J Natl Cancer Inst. 1974 May;52(5):1435–1444. doi: 10.1093/jnci/52.5.1435. [DOI] [PubMed] [Google Scholar]
  16. Piessens W. F., Schur P. H., Moloney W. C., Churchill W. H. Lymphocyte surface immunoglobulins. Distribution and frequency in lymphoproliferative diseases. N Engl J Med. 1973 Jan 25;288(4):176–180. doi: 10.1056/NEJM197301252880403. [DOI] [PubMed] [Google Scholar]
  17. Preud'homme J. L., Seligmann M. Surface bound immunoglobulins as a cell marker in human lymphoproliferative diseases. Blood. 1972 Dec;40(6):777–794. [PubMed] [Google Scholar]
  18. Rowe D. S., Hug K., Forni L., Pernis B. Immunoglobulin D as a lymphocyte receptor. J Exp Med. 1973 Oct 1;138(4):965–972. doi: 10.1084/jem.138.4.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Seligmann M., Preud'Homme J. L., Brouet J. C. B and T cell markers in human proliferative blood diseases and primary immunodeficiencies, with special reference to membrane bound immunoglobulins. Transplant Rev. 1973;16:85–113. doi: 10.1111/j.1600-065x.1973.tb00118.x. [DOI] [PubMed] [Google Scholar]
  20. Wernet P., Feizi T., Kunkel H. G. Idiotypic determinants of immunoglobulin M detected on the surface of human lymphocytes by cytotoxicity assays. J Exp Med. 1972 Sep 1;136(3):650–655. doi: 10.1084/jem.136.3.650. [DOI] [PMC free article] [PubMed] [Google Scholar]

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