Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1973 Dec;15(4):565–572.

Differential asparaginase sensitivity of T-cell and B-cell responses

M C Berenbaum, W A Cope, Wendy Jeffery
PMCID: PMC1553962  PMID: 4591641

Abstract

The effects of L-asparaginase on the T- and B-cell responses to sheep red blood cells and to bacterial lipopolysaccharide were compared in mice. Asparaginase inhibited the response to sheep cells more than the response to lipopolysaccharide. As the former response requires T-cell help whereas the latter does not, this suggests that asparaginase damages T cells more than B cells. However, in vitro, the responses of mouse peripheral blood lymphocytes to phytohaemagglutinin and to lipopolysaccharide were equally sensitive to asparaginase. The relative in vivo resistance of the response to lipopolysaccharide is therefore unlikely to be due to an inherent insensitivity of B cells compared with T cells. It is suggested that the anatomy of lymphoid tissue provides a micro-environment for B cells that partly protects them from the effects of systemic asparagine depletion, whereas the local environment of T cells does not confer such protection.

Full text

PDF
565

Selected References

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

  1. Andersson B., Blomgren H. Evidence for thymus-independent humoral antibody production in mice against polyvinylpyrrolidone and E. coli lipopolysaccharide. Cell Immunol. 1971 Oct;2(5):411–424. doi: 10.1016/0008-8749(71)90052-9. [DOI] [PubMed] [Google Scholar]
  2. Astaldi G., Burgio G. R., Biscatti G., Astaldi A., Jr, Ferfoglia L. L-asparaginase and blastogenesis. Lancet. 1969 Sep 20;2(7621):643–644. doi: 10.1016/s0140-6736(69)90353-5. [DOI] [PubMed] [Google Scholar]
  3. Baldwin R. W., Price M. R., Robins R. A. Blocking of lymphocyte-mediated cytotoxicity for rat hepatoma cells by tumour-specific antigen-antibody complexes. Nat New Biol. 1972 Aug 9;238(84):185–186. doi: 10.1038/newbio238185a0. [DOI] [PubMed] [Google Scholar]
  4. Beard M. E., Crowther D., Galton D. A., Guyer R. J., Fairley G. H., Kay H. E., Knapton P. J., Malpas J. S., Scott R. B. L-asparaginase in treatment of acute leukaemia and lymphosarcoma. Br Med J. 1970 Jan 24;1(5690):191–195. doi: 10.1136/bmj.1.5690.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berenbaum M. C. Immunosuppression by L-asparaginase. Nature. 1970 Feb 7;225(5232):550–552. doi: 10.1038/225550a0. [DOI] [PubMed] [Google Scholar]
  6. Brambilla G., Parodi S., Cavanna M., Caraceni C. E., Baldini L. The immunodepressive activity of Escherichia coli L-asparaginase in some transplantation systems. Cancer Res. 1970 Nov;30(11):2665–2670. [PubMed] [Google Scholar]
  7. Britton S. Regulation of antibody synthesis against Escherichia coli endotoxin. II. Specificity, dose requirements and duration of paralysis induced in adult mice. Immunology. 1969 Apr;16(4):513–526. [PMC free article] [PubMed] [Google Scholar]
  8. Broome J. D. Factors which may influence the effectiveness of L-asparaginases as tumor inhibitors. Br J Cancer. 1968 Sep;22(3):595–602. doi: 10.1038/bjc.1968.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Friedman H. L-asparaginase induced immunosuppression: inhibition of bone marrow derived antibody precursor cells. Science. 1971 Oct 8;174(4005):139–141. doi: 10.1126/science.174.4005.139. [DOI] [PubMed] [Google Scholar]
  10. HILL M. Spontaneous agglutination and haemolysis in acidified serum of erythrocytes from irradiated mice. Nature. 1962 Apr 14;194:199–200. doi: 10.1038/194199b0. [DOI] [PubMed] [Google Scholar]
  11. Hall J. G. The partitioning of L-asparaginase between blood and lymph. Recent Results Cancer Res. 1970;33:75–80. doi: 10.1007/978-3-642-99984-0_10. [DOI] [PubMed] [Google Scholar]
  12. Hamilton-Fairley G., Malpas J. S., Galton D. A. Clinical experience with L-asparaginase. Recent Results Cancer Res. 1970;33:257–262. doi: 10.1007/978-3-642-99984-0_30. [DOI] [PubMed] [Google Scholar]
  13. Ho D. H., Carter C. J., Thetford B., Frei E., 3rd Distribution and mechanism of clearance of L-asparaginase (NSC-109229). Cancer Chemother Rep. 1971 Dec;55(5):539–545. [PubMed] [Google Scholar]
  14. Ho D. H., Whitecar J. P., Jr, Luce J. K., Frei E., 3rd L-asparagine requirement and the effect of L-asparaginase on the normal and leukemic human bone marrow. Cancer Res. 1970 Feb;30(2):466–472. [PubMed] [Google Scholar]
  15. Hobik H. P. Immunosuppressive Wirkung von L-Asparaginase in der Graft-versus-Host-Reaktion. Naturwissenschaften. 1969 Apr;56(4):217–217. doi: 10.1007/BF01166828. [DOI] [PubMed] [Google Scholar]
  16. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  17. Khan A., Hill J. M. Suppression of skin hypersensitivity and antibody formation by L-asparaginase. J Immunol. 1970 Mar;104(3):679–684. [PubMed] [Google Scholar]
  18. Miura M., Kawashima K., Uetani T., Hirano M., Kakizawa H. Influence of L-asparaginase on antibody production and growth of tumors in allogeneic mice. Cancer Res. 1971 Feb;31(2):114–121. [PubMed] [Google Scholar]
  19. Muller-Bérat C. N. Immunosuppressive action of L-asparaginase studied by means of the localized haemolysis in gel assay (L.H.G.A.). Acta Pathol Microbiol Scand. 1969;77(4):750–752. doi: 10.1111/j.1699-0463.1969.tb04517.x. [DOI] [PubMed] [Google Scholar]
  20. Ohno R., Harris J. E., Hersh E. M. L-asparaginase: suppression of the immune response of mice to sheep red blood cells. Clin Exp Immunol. 1970 Aug;7(2):221–227. [PMC free article] [PubMed] [Google Scholar]
  21. Ohno R., Hersh E. M. Immunosuppressive effects of L-asparaginase. Cancer Res. 1970 Jun;30(6):1605–1611. [PubMed] [Google Scholar]
  22. Prager M. D., Bachynsky N. Asparagine synthetase in normal and malignant tissues: correlation with tumor sensitivity to asparaginase. Arch Biochem Biophys. 1968 Sep 20;127(1):645–654. doi: 10.1016/0003-9861(68)90273-7. [DOI] [PubMed] [Google Scholar]
  23. Prager M. D., Derr I. Metabolism of asparagine, aspartate, glutamine, and glutamate in lymphoid tissue: basis for immunosuppression by L-asparaginase. J Immunol. 1971 Apr;106(4):975–979. [PubMed] [Google Scholar]
  24. Quadracci L. J., Hellström I. E., Striker G. E., Marchioro T. L., Hellström K. E. Short communication immune mechanisms in human recipients of renal allografts. Cell Immunol. 1970 Nov;1(5):561–566. doi: 10.1016/0008-8749(70)90042-0. [DOI] [PubMed] [Google Scholar]
  25. Rauenbusch E., Bauer K., Kaufmann W., Wagner O. Isolation and crystallisation of L-asparaginase from E. coli. Recent Results Cancer Res. 1970;33:31–38. doi: 10.1007/978-3-642-99984-0_5. [DOI] [PubMed] [Google Scholar]
  26. Schulten H. K., Giraldo G., Boyse E. A., Oettgen H. F. Immunosuppressive action of L-asparaginase. Lancet. 1969 Sep 20;2(7621):644–645. doi: 10.1016/s0140-6736(69)90354-7. [DOI] [PubMed] [Google Scholar]
  27. Subak-Sharpe H., Bürk R. R., Pitts J. D. Metabolic co-operation between biochemically marked mammalian cells in tissue culture. J Cell Sci. 1969 Mar;4(2):353–367. doi: 10.1242/jcs.4.2.353. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES