Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

In vitro studies of the natural humoral antitumor reactivity of BALB/c and C57BL/6J mice

  • 11 Accesses


Antitumor antibodies were produced in vitro by spleen cells harvested from 12- to 18-month-old C57BL/6J and BALB/c mice with a naturally occurring complement-dependent serum cytotoxicity for tumor cells. The antibodies were of the IgM class and had a complement-dependent cytotoxic reactivity on EL4 cells, which was not absorbed by normal thymus cells. No natural antibodies were produced by untreated spleen cells from 1- or 3-month-old mice of the same two strains, which had no natural serum reactivity. However, after a treatment with an anti-Thy-1 serum and complement before culturing, spleen cells from 3-month-old mice, but not 1-month-old mice, produced the natural antitumor cytotoxic antibodies in vitro. When antibody-producing spleen cells from 12-month-old mice were cultured in vitro together with spleen cells from the unreactive 3-month-old syngeneic mice, inhibition of the antibody production occurred. This inhibiting capacity increased between 1 and 6 months of age and was abrogated by a treatment with an anti-Thy-1 serum and complement or with an anti-Ly-2 serum, whereas the passage of the inhibiting spleen cells on an anti-IgG column did not modify the inhibiting capacity. The in vitro data confirm previous in vivo findings on the nature, specificity and systems of regulation of the natural antitumor cytotoxic antibodies.

This is a preview of subscription content, log in to check access.


  1. 1.

    Aoki T, Boyse EA, Old LJ (1966) Occurrence of natural antibody to the G (Gross) leukemia antigen in mice. Cancer Res 26:1415

  2. 2.

    Boiocchi M, Pierotti MA, Ménard S, Miotti S, Colnaghi MI (1979) Natural antilymphoma antibodies in C3Hf mice serum: Lack of identity with autoimmune and anti murine leukemia virus antibodies. Tumori 65:435

  3. 3.

    Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumor Res 13:1

  4. 4.

    Colnaghi MI, Ménard S (1980) Regulatory role of T suppressor cells on natural and induced humoral antitumor reactivity of C57BL/6J mice. J Immunol 124:2530

  5. 5.

    Colnaghi MI, Ménard S, Della Porta G (1977) Natural anti-tumor serum reactivity in BALB/c mice. II. Control by regulator T-cells. Int J Cancer 19:275

  6. 6.

    Gillette RW, Fox A (1975) The effect of T lymphocyte deficiency on tumor induction and growth. Cell Immunol 19:328

  7. 7.

    Gorer PA, Amos DB (1956) Passive immunity in mice against C57BL leukosis EL4 by means of iso-immune serum. Cancer Res 16:338

  8. 8.

    Haller O, Hansson M, Kiessling R, Wigzell H (1977) Role of non-conventional natural killer cells in resistance against syngeneic tumor cells in vivo. Nature 270:609

  9. 9.

    Herberman RB, Aoki T (1972) Immune and natural antibodies to syngeneic murine plasma cell tumors. J Exp Med 136:94

  10. 10.

    Herberman RB, Holden HT (1979) Natural cell-mediated immunity. Adv Cancer Res 27:305

  11. 11.

    Herberman RB, Nunn ME, Lavrin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer 16:216

  12. 12.

    Ihle JN, Hanna MG Jr (1977) Natural immunity to endogenous oncornavirus in mice. In: Hanna MG, Rapp F (eds) Contemporary topics in immunobiology, vol 6. Plenum Press, New York, pp 169–194

  13. 13.

    Kiessling R, Petranyi G, Klein G, Wigzell H (1975a) Genetic variation of in vitro cytolytic activity and in vivo rejection potential of non-immunized semi-syngeneic mice against a mouse lymphoma line. Int J Cancer 15:933

  14. 14.

    Kiessling R, Klein E, Pross H, Wigzell H (1975b) Natural killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell. Eur J Immunol 5:117

  15. 15.

    Klein E, Masucci MG, Masucci G, Vanky F (to be published) Natural and activated lymphocyte killers which affect tumor cells. In: Natural cell mediated immunity against tumors. Academic Press, New York

  16. 16.

    Martin WJ, Martin SE (1974) Naturally occurring cytotoxic antitumor antibodies in sera of congenitally athymic (nude) mice. Nature 249:564

  17. 17.

    Martin SE, Martin WJ (1975) Anti-tumor antibodies in normal mouse sera. Int J Cancer 15:658

  18. 18.

    Ménard S, Colnaghi MI, Della Porta G (1977) Natural antitumor serum reactivity in BALB/c mice. I. Characterization and interference with tumor growth. Int J Cancer 19:267

  19. 19.

    Ménard S, Colnaghi MI, Della Porta G (1980) Comparison of the natural humoral antitumor reactivity of different strains of mice. Tumori 66:13

  20. 20.

    Outzen HC, Custer RP, Eaton GJ, Prehn RT (1975) Spontaneous and induced tumor incidence in germ-free “nude” mice. J Reticuloendothel Soc 17:1

  21. 21.

    Pierotti MA, Colnaghi MI (1975) Natural antibodies directed against murine lymphosarcoma cells. J Natl Cancer Inst 55:945

  22. 22.

    Pierotti MA, Miotti S, Della Torre G, Colnaghi MI (1976) Nature and properties of C3Hf natural antitumor cytotoxins directed against murine lymphosarcoma cells. Tumori 62:545

  23. 23.

    Riccardi C, Santoni A, Barlozzari T, Puccetti P, Herberman RB (1980) In vivo natural reactivity of mice against tumor cells. Int J Cancer 25:475

  24. 24.

    Rygaard J, Povlsen CO (1976) The nude mouse vs the hypothesis of immunological surveillance. Transplant Rev 28:43

  25. 25.

    Schacter B, Bias WB, Humphrey RL (1976) Normal human sera cytotoxic to cells of human acute leukemia. Tissue Antigens 8:289

  26. 26.

    Simpson E, Nehlson SL (1971) Prolonged administration of antithymocyte serum in mice. II. Histopathological investigations. Clin Exp Immunol 9:79

  27. 27.

    Stutman O (1974) Tumour development after 3-methylcholanthrene in immunologically deficient athymic-nude mice. Science 183:534

Download references

Author information

Correspondence to Sylvie Ménard.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ménard, S., Colnaghi, M.I. In vitro studies of the natural humoral antitumor reactivity of BALB/c and C57BL/6J mice. Cancer Immunol Immunother 10, 139–146 (1981). https://doi.org/10.1007/BF00205885

Download citation


  • Tumor Cell
  • Cancer Research
  • Vitro Study
  • Spleen Cell
  • Antibody Production