Skip to main content
PMC 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
. 1978 Nov;75(11):5706–5710. doi: 10.1073/pnas.75.11.5706

Lymphoblastoid cell lines from patients with chronic lymphocytic leukemia: identification of tumor origin by idiotypic analysis.

J N Hurley, S M Fu, H G Kunkel, G McKenna, M D Scharff
PMCID: PMC393037  PMID: 82971

Abstract

Multiple lymphoblastoid cell lines have been derived from two patients with chronic lymphocytic leukemia with an associated monoclonal immunoglobulin (Ig) band. Idiotypic antisera raised against the monoclonal serum Ig bands were shown to be specific for the membrane Ig of the patients' leukemic cells. The idiotypic determinants in these patients thereby constitute tumor-specific antigens. Surface and intracellular immunofluorescence studies utilizing these idiotypic antisera were used to identify the cell lines of leukemic origin. These studies showed that certain cell lines from each patient were derived from the leukemic cells while other cell lines were derived from residual normal B lymphocytes. The leukemic cell lines were variable and contained different percentages of lymphoid cells with the idiotype-specific membrane Ig and, in addition, different percentages of plasma cells with intracellular Ig of the same specificity. Specific Ig synthesis was also demonstrated by hemagglutination-inhibition analysis of cell line supernatants. Aside from Ig specificity, no differences have been found between the leukemic cell lines and those derived from normal cells. One of the leukemic cell lines was cloned in soft agarose. All the clones were shown to be of leukemic origin.

Full text

PDF
5706

Images in this article

5708Image
on p.5708

Selected References

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

  1. AZAR H. A., HILL W. T., OSSERMAN E. F. Malignant lymphoma and lymphatic leukemia associated with myeloma-type serum proteins. Am J Med. 1957 Aug;23(2):239–249. doi: 10.1016/0002-9343(57)90197-3. [DOI] [PubMed] [Google Scholar]
  2. Belpomme D., Minowada J., Moore G. E. Are some human lymphoblastoid cell lines established from leukemic tissues actually derived from normal leukocytes? Cancer. 1972 Jul;30(1):282–287. doi: 10.1002/1097-0142(197207)30:1<282::aid-cncr2820300139>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  3. Buell D. N., Fahey J. L. Limited periods of gene expression in immunoglobulin-synthesizing cells. Science. 1969 Jun 27;164(3887):1524–1525. doi: 10.1126/science.164.3887.1524. [DOI] [PubMed] [Google Scholar]
  4. Coffino P., Baumal R., Laskov R., Scharff M. D. Cloning of mouse myeloma cells and detection of rare variants. J Cell Physiol. 1972 Jun;79(3):429–440. doi: 10.1002/jcp.1040790313. [DOI] [PubMed] [Google Scholar]
  5. Epstein A. L., Kaplan H. S. Biology of the human malignant lymphomas. I. Establishment in continuous cell culture and heterotransplantation of diffuse histiocytic lymphomas. Cancer. 1974 Dec;34(6):1851–1872. doi: 10.1002/1097-0142(197412)34:6<1851::aid-cncr2820340602>3.0.co;2-4. [DOI] [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. Fu S. M., Winchester R. J., Kunkel H. G. Similar idiotypic specificity for the membrane IgD and IgM of human B lymphocytes. J Immunol. 1975 Jan;114(1 Pt 1):250–252. [PubMed] [Google Scholar]
  8. Hough D. W., Eady R. P., Hamblin T. J., Stevenson F. K., Stevenson G. T. Anti-idiotype sera raised against surface immunoglobulin of human neoplastic lymphocytes. J Exp Med. 1976 Oct 1;144(4):960–969. doi: 10.1084/jem.144.4.960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. KAPLOW L. S. SIMPLIFIED MYELOPEROXIDASE STAIN USING BENZIDINE DIHYDROCHLORIDE. Blood. 1965 Aug;26:215–219. [PubMed] [Google Scholar]
  10. Kaplan J., Shope T. C., Peterson W. D., Jr Epstein-barr virus-negative human malignant T-cell lines. J Exp Med. 1974 May 1;139(5):1070–1076. doi: 10.1084/jem.139.5.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kwok S. Y., Litwin S. D. Immunoglobulin expression of cells from human lymphoblastoid lines. III. Cell cycle phase and surface immunoglobulin expression. Cell Immunol. 1976 Aug;25(2):256–265. doi: 10.1016/0008-8749(76)90116-7. [DOI] [PubMed] [Google Scholar]
  12. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  13. Miller G., Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A. 1973 Jan;70(1):190–194. doi: 10.1073/pnas.70.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Natvig J. B., Kunkel H. G. Detection of genetic antigens utilizing gamma globulins coupled to red blood cells. Nature. 1967 Jul 1;215(5096):68–69. doi: 10.1038/215068a0. [DOI] [PubMed] [Google Scholar]
  15. Nilsson K., Pontén J. Classification and biological nature of established human hematopoietic cell lines. Int J Cancer. 1975 Feb 15;15(2):321–341. doi: 10.1002/ijc.2910150217. [DOI] [PubMed] [Google Scholar]
  16. Nilsson K., Sundström C. Establishment and characteristics of two unique cell lines from patients with lymphosarcoma. Int J Cancer. 1974 Jun 15;13(6):808–823. doi: 10.1002/ijc.2910130609. [DOI] [PubMed] [Google Scholar]
  17. Reedman B. M., Klein G. Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer. 1973 May;11(3):499–520. doi: 10.1002/ijc.2910110302. [DOI] [PubMed] [Google Scholar]
  18. Rosenfeld C., Goutner A., Choquet C., Venuat A. M., Kayibanda B., Pico J. L., Greaves M. F. Phenotypic characterisation of a unique non-T, non-B acute lymphoblastic leukaemia cell line. Nature. 1977 Jun 30;267(5614):841–843. doi: 10.1038/267841a0. [DOI] [PubMed] [Google Scholar]
  19. Sawitsky B., Douglas S. D., Lipton R., Sawitsky A. Biochemical and morphological observations on lymphocytes in continuous cell culture from a patient with chronic lymphocytic leukemia. Acta Haematol. 1974;52(2):83–94. doi: 10.1159/000208225. [DOI] [PubMed] [Google Scholar]
  20. Saxon A., Stevens R. H., Quan S. G., Golde D. W. Immunologic characterization of hairy cell leukemias in continuous culture. J Immunol. 1978 Mar;120(3):777–782. [PubMed] [Google Scholar]
  21. Takahashi M., Yagi Y., Moore G. E., Pressman D. Immunoglobulin production in synchronized cultures of human hematopoietic cell lines. I. Variation of cellular immunoglobulin level with the generation cycle. J Immunol. 1969 Oct;103(4):834–843. [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