Skip to main content
Immunology logoLink to Immunology
. 1976 Sep;31(3):433–441.

Differentiation of lymphoid cells: the non-mitogenic induction of immunoglobulin production by thymus cell extract and thymus cell culture filtrate.

N Shinohara, K Okumura, M Kern
PMCID: PMC1445232  PMID: 1088422

Abstract

The cell-free medium in which thymocytes have been cultured (filtrate) as well as sonic lysates of thymocytes (extract) enhance immunoglobulin production when added to spleen cells during tissue culture. In spite of the requirement for foetal calf serum in the culture medium, production of the enhancing factor in thymocyte culture filtrates occurred even in the presence of a variety of metabolic inhibitors including NaN3, puromycin and hydroxyurea. Although DNA synthesis is required as a prelude to the induction of immunoglobulin production, two lines of evidence indicate that the enhancement produced in response to filtrate and extract occurs via a non-mitogenic process. First, neither cell-free agent was mitogenic toward spleen cells. Secondly, the enhancement of immunoglobulin production due to filtrate or extract was observed even in the presence of inhibitors of DNA synthesis. Multiple functions for thymocytes in the induction of immunoglobulin production are indicated by the findings that thymocytes restore immunoglobulin production of anti-thymocyte serum-treated spleen cells, whereas filtrate and extract, alone or in combination, do not have this capability. Furthermore, filtrate and extract failed to enhance the induction of DNP-group-specific antibody production by cells incubated with DNP-protein, but filtrate and extract could partially restore anti-DNP antibody production of such anti-thymocyte serum-treated cells. The role of thymocytes, filtrate and extract in the antigen-independent and the antigen-dependent induction of immunoglobulin production is discussed.

Full text

PDF
433

Selected References

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

  1. Andersson J., Sjöberg O., Möller G. Mitogens as probes for immunocyte activation and cellular cooperation. Transplant Rev. 1972;11:131–177. doi: 10.1111/j.1600-065x.1972.tb00048.x. [DOI] [PubMed] [Google Scholar]
  2. Askonas B. A., Schimpl A., Wecker E. The differentiation function of T cell-replacing factor in nu-nu spleen cell cultures. Eur J Immunol. 1974 Mar;4(3):164–169. doi: 10.1002/eji.1830040304. [DOI] [PubMed] [Google Scholar]
  3. Claman H. N., Chaperon E. A. Immunologic complementation between thymus and marrow cells--a model for the two-cell theory of immunocompetence. Transplant Rev. 1969;1:92–113. doi: 10.1111/j.1600-065x.1969.tb00137.x. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Doria G., Agarossi G., Di Pietro S. Enhancing activity of thymocyte culture cell-free medium on the in vitro immune response of spleen cells from neonatally thymectomized mice to sheep RBC. J Immunol. 1972 Jan;108(1):268–270. [PubMed] [Google Scholar]
  6. Feldmann M., Basten A. Cell interactions in the immune response in vitro. 3. Specific collaboration across a cell impermeable membrane. J Exp Med. 1972 Jul 1;136(1):49–67. doi: 10.1084/jem.136.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feldmann M., Basten A. Cell interactions in the immune response in vitro. IV. Comparison of the effects of antigen-specific and allogeneic thymus-derived cell factors. J Exp Med. 1972 Oct 1;136(4):722–736. doi: 10.1084/jem.136.4.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gold E. R., Fudenberg H. H. Chromic chloride: a coupling reagent for passive hemagglutination reactions. J Immunol. 1967 Nov;99(5):859–866. [PubMed] [Google Scholar]
  9. HELMREICH E., KERN M., EISEN H. N. The secretion of antibody by isolated lymph node cells. J Biol Chem. 1961 Feb;236:464–473. [PubMed] [Google Scholar]
  10. Katz D. H., Benacerraf B. The regulatory influence of activated T cells on B cell responses to antigen. Adv Immunol. 1972;15:1–94. doi: 10.1016/s0065-2776(08)60683-5. [DOI] [PubMed] [Google Scholar]
  11. Kern M., Helmreich E., Eisen H. N. A DEMONSTRATION OF ANTIBODY ACTIVITY ON MICROSOMES. Proc Natl Acad Sci U S A. 1959 Jun;45(6):862–867. doi: 10.1073/pnas.45.6.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kishimoto T., Ishizaka K. Regulation of antibody response in vitro. VII. Enhancing soluble factors for IgG and IgE antibody response. J Immunol. 1973 Oct;111(4):1194–1205. [PubMed] [Google Scholar]
  13. Maillard J., Bloom B. R. Immunological adjuvants and the mechanism of cell cooperation. J Exp Med. 1972 Jul 1;136(1):185–190. doi: 10.1084/jem.136.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller J. F., Mitchell G. F. Thymus and antigen-reactive cells. Transplant Rev. 1969;1:3–42. doi: 10.1111/j.1600-065x.1969.tb00135.x. [DOI] [PubMed] [Google Scholar]
  15. Okumura K., Kern M. The absolute requirement for T-cells in the induction of IgM-secreting cells, in vitro. Ann N Y Acad Sci. 1975 Feb 28;249:477–483. doi: 10.1111/j.1749-6632.1975.tb29096.x. [DOI] [PubMed] [Google Scholar]
  16. Okumura K., Shinoara N., Kern M. Differentiation of lymphoid cells: enhancement of the induction of immunoglobulin production by thymus cells and a product secreted by thymus cells. J Immunol. 1974 Dec;113(6):2027–2034. [PubMed] [Google Scholar]
  17. Rubin A. S., Coons A. H. Specific heterologous enhancement of immune responses. 3. Partial characterization of supernatant material with enhancing activity. J Immunol. 1972 Jun;108(6):1597–1604. [PubMed] [Google Scholar]
  18. Schimpl A., Wecker E. A third signal in B cell activation given by TRF. Transplant Rev. 1975;23:176–188. doi: 10.1111/j.1600-065x.1975.tb00157.x. [DOI] [PubMed] [Google Scholar]
  19. Sutherland E. W., 3rd, Zimmerman D. H., Kern M. Synthesis and secretion of gamma-globulin by lymph node cells, VIII. Order of synthesis of the interchain disulfide linkages of immunoglobulins. Proc Natl Acad Sci U S A. 1970 Jul;66(3):987–994. doi: 10.1073/pnas.66.3.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Swenson R. M., Kern M. THE SYNTHESIS AND SECRETION OF gamma-GLOBULINS BY LYMPH NODE CELLS, I. THE MICROSOMAL COMPARTMENTALIZATION OF gamma-GLOBULINS. Proc Natl Acad Sci U S A. 1967 Feb;57(2):417–422. doi: 10.1073/pnas.57.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Takahashi T., Old L. J., Boyse E. A. Surface alloantigens of plasma cells. J Exp Med. 1970 Jun 1;131(6):1325–1341. doi: 10.1084/jem.131.6.1325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Taniguchi M., Tada T. Regulation of homocytotropic antibody formation in the rat. X. IgT-like molecule for the induction of homocytotropic antibody response. J Immunol. 1974 Dec;113(6):1757–1769. [PubMed] [Google Scholar]
  23. Taussig M. J. T cell factor which can replace T cells in vivo. Nature. 1974 Mar 15;248(445):234–236. doi: 10.1038/248234a0. [DOI] [PubMed] [Google Scholar]
  24. Zimmerman D. H., Kern M. Differentiation of lymphoid cells: effect of serum and other mitogenic agents on the selective induction of immunoglobulin M secreting lymph node cells in tissue culture. J Immunol. 1973 Nov;111(5):1326–1333. [PubMed] [Google Scholar]
  25. Zimmerman D. H., Kern M. Differentiation of lymphoid cells: the in vitro emergence of immunoglobulin M-secreting cells. J Immunol. 1973 Sep;111(3):761–769. [PubMed] [Google Scholar]
  26. Zimmerman D. H., Okumura K., Rabkin C., Kern M. Differentiation of lymphoid cells: the use of specific antisera to characterize the cells required for the induction of immunoglobulin M production in vitro. J Immunol. 1974 Dec;113(6):1891–1896. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES