Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1974 Aug 1;140(2):333–348. doi: 10.1084/jem.140.2.333

CHARACTERISTICS OF IMMUNOLOGICAL MEMORY IN MICE

I. SEPARATE EARLY GENERATION OF CELLS MEDIATING IGM AND IGG MEMORY TO SHEEP ERYTHROCYTES

S J Black 1, C J Inchley 1
PMCID: PMC2139600  PMID: 4602981

Abstract

The kinetics of the generation of primed IgM and IgG antibody-forming cell precursors, and of helper T-cell populations, were analyzed in mice whose primary responses to high and low doses of SRBC were arrested at intervals by the immunosuppressive agents cyclophosphamide monohydrate and specific antibody. The extent to which immunological memory was established in these animals before blockade of the primary response was assessed by the hemolytic plaque assay following challenge 12 wk after priming. The presence of IgG B-memory cells and T-memory cells in suppressed mice was further investigated by the transfer into these animals of syngeneic SRBC-stimulated thymocytes or anti-θ-treated spleen cells. It was found that the progenitors of secondary IgM-synthesizing cells were primed almost immediately after injection of antigen, and that early blockade of the primary response resulted in a raised IgM response after challenge. On the other hand, priming for a secondary IgG response took at least 4 days, and was dose-dependent, although helper T populations for a secondary IgG response appeared 3 days after antigen injection. It appeared that both IgM and IgG memory cells may be considered as Y cells in terms of the X-Y-Z scheme of lymphocyte activation, but that the two populations are generated at different times after exposure to antigen. The size of either Y-cell population at any given time is dependent upon the amount of antigen available to provoke differentiation to antibody-forming Z cells, and the IgM Y-cell population in particular is likely to be depleted during the course of a normal 1° response. When IgM Y cells were maintained for long periods as a result of immunosuppression, their secondary antibody response was independent of the primed T cells necessary for a secondary IgG response.

Full Text

The Full Text of this article is available as a PDF (830.4 KB).

Selected References

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

  1. Celada F. The cellular basis of immunologic memory. Prog Allergy. 1971;15:223–267. [PubMed] [Google Scholar]
  2. Cerottini J. C., Trnka Z. The role of persisting antigen in the development of immunological memory. Int Arch Allergy Appl Immunol. 1970;38(1):37–41. doi: 10.1159/000230257. [DOI] [PubMed] [Google Scholar]
  3. Cohen J. J., Claman H. N. Thymus-marrow immunocompetence. V. Hydrocortisone-resistant cells and processes in the hemolytic antibody response of mice. J Exp Med. 1971 May 1;133(5):1026–1034. doi: 10.1084/jem.133.5.1026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cunningham A. J. Studies on the cellular basis of IgM immunological memory. The induction of antibody formation in bone marrow cells by primed spleen cells. Immunology. 1969 Dec;17(6):933–942. [PMC free article] [PubMed] [Google Scholar]
  5. Cunningham A. J. Studies on the cellular basis of IgM immunological memory. Immunology. 1969 May;16(5):621–632. [PMC free article] [PubMed] [Google Scholar]
  6. Elkins W. L. Specific and nonspecific lymphoid cell proliferation in the pathogenesis of graft-versus-host reactions. Transplantation. 1970 Mar;9(3):273–301. doi: 10.1097/00007890-197003000-00011. [DOI] [PubMed] [Google Scholar]
  7. Feldbush T. L. Antigen modulation of the immune response. The decline of immunological memory in the absence of continuing antigenic stimulation. Cell Immunol. 1973 Sep;8(3):435–444. doi: 10.1016/0008-8749(73)90134-2. [DOI] [PubMed] [Google Scholar]
  8. HUGHES W. L., COMMERFORD S. L., GITLIN D., KRUEGER R. C., SCHULTZE B., SHAH V., REILLY P. DEOXYRIBONUCLEIC ACID METABOLISM IN VIVO: I. CELL PROLIFERATION AND DEATH AS MEASURED BY INCORPORATION AND ELIMINATION OF IODODEOXYURIDINE. Fed Proc. 1964 May-Jun;23:640–648. [PubMed] [Google Scholar]
  9. Hanna M. G., Jr, Nettesheim P., Francis M. W. Requirement for continuous antigenic stimulation in the development and differentiation of antibody-forming cells. The effect of passive antibody on the primary and secondary response. J Exp Med. 1969 May 1;129(5):953–971. doi: 10.1084/jem.129.5.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Many A., Schwartz R. S. On the mechanism of immunological tolerance in cyclophosphamide-treated mice. Clin Exp Immunol. 1970 Jan;6(1):87–99. [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Mitchell G. F., Chan E. L., Noble M. S., Weissman I. L., Mishell R. I., Herzenberg L. A. Immunological memory in mice. 3. Memory to heterologous erythrocytes in both T cell and B cell populations and requirement for T cells in expression of B cell memory. Evidence using immunoglobulin allotype and mouse alloantigen theta markers with congenic mice. J Exp Med. 1972 Feb 1;135(2):165–184. doi: 10.1084/jem.135.2.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nakamura I., Segal S., Globerson A., Feldman M. DNA replication as a prerequisite for the induction of primary antibody response. Cell Immunol. 1972 Aug;4(4):351–366. doi: 10.1016/0008-8749(72)90038-x. [DOI] [PubMed] [Google Scholar]
  14. Nossal G. J., Austin C. M., Ada G. L. Antigens in immunity. VII. Analysis of immunological memory. Immunology. 1965 Oct;9(4):333–348. [PMC free article] [PubMed] [Google Scholar]
  15. Pritchard H., Micklem H. S. Immune responses in congenitally thymus-less mice. I. Absence of response to oxazolone. Clin Exp Immunol. 1972 Jan;10(1):151–161. [PMC free article] [PubMed] [Google Scholar]
  16. Pritchard H., Riddaway J., Micklem H. S. Immune responses in congenitally thymus-less mice. II. Quantitative studies of serum immunoglobulins, the antibody response to sheep erythrocytes, and the effect of thymus allografting. Clin Exp Immunol. 1973 Jan;13(1):125–138. [PMC free article] [PubMed] [Google Scholar]
  17. REIF A. E., ALLEN J. M. THE AKR THYMIC ANTIGEN AND ITS DISTRIBUTION IN LEUKEMIAS AND NERVOUS TISSUES. J Exp Med. 1964 Sep 1;120:413–433. doi: 10.1084/jem.120.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Safford J. W., Jr, Tokuda S. Antibody-mediated suppression of the immune response: effect on the development of immunologic memory. J Immunol. 1971 Nov;107(5):1213–1225. [PubMed] [Google Scholar]
  19. Segal S., Globerson A., Feldman M. A bicellular mechanism in the immune response to chemically defined antigens. I. Antibody formation in vitro. Cell Immunol. 1971 Jun;2(3):205–221. doi: 10.1016/0008-8749(71)90040-2. [DOI] [PubMed] [Google Scholar]
  20. Sercarz E. E., Byers V. S. The X-Y-Z scheme of immunocyte maturation. 3. Early IgM memory and the nature of the memory cell. J Immunol. 1967 Apr;98(4):836–843. [PubMed] [Google Scholar]
  21. Sprent J., Miller J. F., Mitchell G. F. Antigen-induced selective recruitment of circulating lymphocytes. Cell Immunol. 1971 Apr;2(2):171–181. doi: 10.1016/0008-8749(71)90036-0. [DOI] [PubMed] [Google Scholar]
  22. Taylor R. B., Wortis H. H. Thymus dependence of antibody response: variation with dose of antigen and class of antibody. Nature. 1968 Nov 30;220(5170):927–928. doi: 10.1038/220927a0. [DOI] [PubMed] [Google Scholar]
  23. Uhr J. W., Möller G. Regulatory effect of antibody on the immune response. Adv Immunol. 1968;8:81–127. doi: 10.1016/s0065-2776(08)60465-4. [DOI] [PubMed] [Google Scholar]
  24. Wigzell H. The rise and fall of 19S immunological memory against sheep red cells in the mouse. Ann Med Exp Biol Fenn. 1966;44(2):209–215. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES