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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 Dec;75(12):6211–6214. doi: 10.1073/pnas.75.12.6211

Leukemia in AKR mice: A defined suppressor cell population expressing membrane-associated DNA

James L Russell 1, Edward S Golub 1
PMCID: PMC393149  PMID: 366615

Abstract

Leukemic AKR mouse spleen cells suppress normal AKR anti-sheep erythrocyte antibody responses in vitro. Treatment of leukemic spleen cells with DNase I prior to coculture with normal AKR cells abrogates their suppressive ability. Treatment of leukemic cells with a wide range of DNase I concentrations has no effect on the viability of these cells as measured by incorporation of [3H]thymidine or by eosin dye exclusion. When the activating divalent cations required for DNase I action are functionally removed in the enzyme treatment medium by chelation with EDTA, the ability of DNase I to abrogate suppression is abolished. Furthermore, the effects of DNase I in overcoming suppression are not able to be mimicked by trypsin, Pronase, or ribonuclease. These results are consistent with the existence of a population of cells in the leukemic spleen that expresses a form of membrane-associated DNA that functions in the suppression of normal antibody responses. The existence of such a population was shown by treating leukemic spleen cells with anti-single-stranded-DNA and then passing them through an anti-immunoglobulin immunoadsorption column. Approximately 15% of the leukemic cells are retained on the column and can be specifically eluted with the normal immunoglobulin. The cells of this enriched population when cocultured with normal spleen cells exhibit a 10-fold greater suppressive ability than unfractionated cells. Thus, there exists in the spleens of overtly leukemic AKR mice a population of cells expressing a form of DNA on their surfaces that in some manner is necessary for immunosuppression.

Keywords: cell chromatography, anti-DNA, suppression, in vitro antibody synthesis

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Selected References

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

  1. ASHLEY F. L., McNALL E. G., DUTT N. R., GARCIA E. N., SLOAN R. F. The effects of nucleic acids on homograft tolerance. Ann N Y Acad Sci. 1960 May 31;87:429–444. doi: 10.1111/j.1749-6632.1960.tb23210.x. [DOI] [PubMed] [Google Scholar]
  2. Colmerauer M. E., Rumi L., Saal F., Pasqualini C. D., Rabasa S. L. RNA-mediated immunologic depression. J Immunol. 1973 Sep;111(3):743–749. [PubMed] [Google Scholar]
  3. Cunningham A. J., Szenberg A. Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology. 1968 Apr;14(4):599–600. [PMC free article] [PubMed] [Google Scholar]
  4. Fournié G. J., Lambert P. H., Meischer P. A. Release of DNA in circulating blood and induction of anti-DNA antibodies after injection of bacterial lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1189–1206. doi: 10.1084/jem.140.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Golub E. S. Brain-associated theta antigen: reactivity of rabbit anti-mouse brain with mouse lymphoid cells. Cell Immunol. 1971 Aug;2(4):353–361. doi: 10.1016/0008-8749(71)90070-0. [DOI] [PubMed] [Google Scholar]
  6. Harris G., Pelc S. R., Blackmore D. K. Synthesis of DNA by the spleens of germ-free mice during the primary response to sheep red cells. Eur J Immunol. 1973 Feb;3(2):103–108. doi: 10.1002/eji.1830030210. [DOI] [PubMed] [Google Scholar]
  7. Hill M., Hillova J. Recombinational events between exogenous mouse DNA and newly synthesized DNA strands of chicken cells in culture. Nat New Biol. 1971 Jun 30;231(26):261–265. doi: 10.1038/newbio231261a0. [DOI] [PubMed] [Google Scholar]
  8. Hill M., Huppert J. Fate of exogenous mouse DNA in chicken fibroblasts in vitro. Non-conservative preservation. Biochim Biophys Acta. 1970 Jul 16;213(1):26–35. doi: 10.1016/0005-2787(70)90004-3. [DOI] [PubMed] [Google Scholar]
  9. Hill M. The uptake of deoxyribonucleic acid released from damaged cells in tissue cultures. Exp Cell Res. 1967 Mar;45(3):533–549. doi: 10.1016/0014-4827(67)90158-9. [DOI] [PubMed] [Google Scholar]
  10. LOWE M. L., AXELROD A. E. STUDIES ON SPECIFICITY OF ACTION OF RIBONUCLEIC ACID EXTRACTS UPON VIABILITY OF SKIN HOMOGRAFTS IN THE RAT. Transplantation. 1964 Jan;2:82–86. doi: 10.1097/00007890-196401000-00009. [DOI] [PubMed] [Google Scholar]
  11. Ledoux L., Charles P. Uptake of exogenous DNA by mouse embryos. Exp Cell Res. 1967 Feb;45(2):498–501. doi: 10.1016/0014-4827(67)90200-5. [DOI] [PubMed] [Google Scholar]
  12. Lerner R. A., Meinke W., Goldstein D. A. Membrane-associated DNA in the cytoplasm of diploid human lymphocytes. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1212–1216. doi: 10.1073/pnas.68.6.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morini J. C., Londner M. V., Font M. T., Rabasa S. L. Effect of immune and normal RNA on the immunological response induced by rat red blood cells. Experientia. 1969 Jun 15;25(6):640–641. doi: 10.1007/BF01896565. [DOI] [PubMed] [Google Scholar]
  15. Mulder A. M., Durdik J. M., Toth P., Golub E. S. Leukemia in AKR mice. III. Size distribution of suppressor T-cells in AKR leukemia and neonatal mice. Cell Immunol. 1978 Oct;40(2):326–335. doi: 10.1016/0008-8749(78)90340-4. [DOI] [PubMed] [Google Scholar]
  16. Olsen I., Harris G. Uptake and release of DNA by lymphoid tissue and cells. Immunology. 1974 Dec;27(6):973–987. [PMC free article] [PubMed] [Google Scholar]
  17. PELC S. R. LABELLING OF DNA AND CELL DIVISION IN SO CALLED NON-DIVIDING TISSUES. J Cell Biol. 1964 Jul;22:21–28. doi: 10.1083/jcb.22.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. PLESCIA O. J., BRAUN W., PALCZUK N. C. PRODUCTION OF ANTIBODIES TO DENATURED DEOXYRIBONUCLEIC ACID (DNA). Proc Natl Acad Sci U S A. 1964 Aug;52:279–285. doi: 10.1073/pnas.52.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pelc S. R., Harris G., Caldwell I. The relationship between antibody formation and deoxyribonucleic acid (DNA) synthesis in mouse spleen during primary and secondary response to sheep erythrocytes (SRC). Immunology. 1972 Aug;23(2):183–197. [PMC free article] [PubMed] [Google Scholar]
  20. Rogers J. C., Boldt D., Kornfeld S., Skinner A., Valeri C. R. Excretion of deoxyribonucleic acid by lymphocytes stimulated with phytohemagglutinin or antigen. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1685–1689. doi: 10.1073/pnas.69.7.1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Roman J. M., Golub E. S. Leukemia in AKR mice. I. Effects of leukemic cells on antibody-forming potential of syngeneic and allogeneic normal cells. J Exp Med. 1976 Mar 1;143(3):482–496. doi: 10.1084/jem.143.3.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roman J. M., Golub E. S. Leukemia in AKR mice. II. Two modes of suppression of in vitro antibody formation by leukemic cells. Cell Immunol. 1978 Oct;40(2):316–325. doi: 10.1016/0008-8749(78)90339-8. [DOI] [PubMed] [Google Scholar]
  23. TRAKATELLIS A. C., AXELROD A. E., MONTJAR M., LAMY F. INDUCTION OF IMMUNE TOLERANCE WITH RIBOSOMES AND RIBONUCLEIC ACID EXTRACTS IN NEW-BORN MICE. Nature. 1964 Apr 11;202:154–157. doi: 10.1038/202154a0. [DOI] [PubMed] [Google Scholar]

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