Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1982 Jul;49(1):87–95.

Lymphocyte subpopulations in the thymus of NZB x NZW mice: phenotypic characterization by flow cytofluorometry analysis.

F Dumont, R C Habbersett
PMCID: PMC1536656  PMID: 6982134

Abstract

The composition of the thymocyte population was investigated as a function of age in the autoimmunity-prone NZB x NZW F1 (NZB x W) female mice and in control BALB/c female mice. Single- and two-colour flow cytofluorometry analyses were used to quantitate the cell surface binding of fluorochrome-conjugated antibodies directed against various lymphocyte markers and of fluoresceinated peanut agglutinin (PNA). In both mouse strains, two major phenotypically distinct thymocyte subpopulations were thus identified. The predominant subpopulation was characterized as bright Thy-1+, Lyt-1 + 2+ and bright PNA+, and the other one as dull Thy-1+, Lyt-1 + 2- and dull PNA+. The relative frequencies of these two subpopulations were similar in NZB x W and BALB/c mice at 3 months of age. However, from 6 months onwards, slight but significant differences became detectable between the two strains. Thus, in BALB/c mice, both thymocyte subpopulations regressed at approximately the same rate during ageing so that their relative proportions remained constant. In contrast, in NZB x W mice, while the number of bright Thy-1+ cells diminished as in BALB/c mice, the number of dull Thy-1+ cells barely varied from 3 to 12 months of age, which resulted in a proportional increase of this latter subpopulation. Moreover, elevated frequencies of surface immunoglobulin-bearing cells were recorded in the thymus of 8-12 month old NZB x W mice but not in BALB/c mice. Therefore, the development of autoimmunity in NZB x W mice appears associated with an abnormal age-dependent evolution of the intrathymic lymphocyte population.

Full text

PDF
87

Selected References

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

  1. Bach J. F., Dardenne M., Salomon J. C. Studies on thymus products. IV. Absence of serum 'thymic activity' in adult NZB and (NZB x NZW) F1 mice. Clin Exp Immunol. 1973 Jun;14(2):247–256. [PMC free article] [PubMed] [Google Scholar]
  2. Ben-Yaakov M., Haran-Ghera N. T & B lymphocytes in thymus of SJL/J mice. Nature. 1975 May 1;255(5503):64–66. doi: 10.1038/255064a0. [DOI] [PubMed] [Google Scholar]
  3. Betel I., Mathieson B. J., Sharrow S. O., Asofsky R. Distribution of Lyt phenotypes in thymocyte subpopulations as measured by flow microfluorometry: selective enrichment of Lyt 1+23- thymocytes. J Immunol. 1980 May;124(5):2209–2217. [PubMed] [Google Scholar]
  4. Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dumont F. Lymphocyte subpopulations in the thymus of SJL/J mice: age-related alterations and the effect of spontaneous reticulum cell sarcoma development. J Clin Lab Immunol. 1980 Jan;3(1):51–61. [PubMed] [Google Scholar]
  6. Dumont F., Robert F., Gerard H. Abnormalities of the thymus in aged female (NZB x SJL)F1 mice: separation and characterization of intrathymic T cells, B cells, and plasma cells. J Immunol. 1981 Jun;126(6):2450–2456. [PubMed] [Google Scholar]
  7. Fowlkes B. J., Waxdal M. J., Sharrow S. O., Thomas C. A., 3rd, Asofsky R., Mathieson B. J. Differential binding of fluorescein-labeled lectins to mouse thymocytes: subsets revealed by flow microfluorometry. J Immunol. 1980 Aug;125(2):623–630. [PubMed] [Google Scholar]
  8. Gerber N. L., Hardin J. A., Chused T. M., Steinberg A. D. Loss with age in NZB-W mice of thymic suppressor cells in the graft-vs-host reaction. J Immunol. 1974 Nov;113(5):1618–1625. [PubMed] [Google Scholar]
  9. Gershwin M. E., Ikeda R. M., Kruse W. L., Wilson F., Shifrine M., Spangler W. Age-dependent loss in New Zealand mice of morphological and functional characteristics of thymic epithelial cells. J Immunol. 1978 Mar;120(3):971–979. [PubMed] [Google Scholar]
  10. Greenspan J. S., Gutman G. A., Talal N., Weissman I. L., Sugai S. Thymus-antigen- and immunoglobulin- positive cells in lymph-nodes, thymus, and malignant lymphomas of NZB/NZW mice. Clin Immunol Immunopathol. 1974 Sep;3(1):32–51. doi: 10.1016/0090-1229(74)90021-x. [DOI] [PubMed] [Google Scholar]
  11. HELYER B. J., HOWIE J. B. Renal disease associated with positive lupus erythematosus tests in a cross-bred strain of mice. Nature. 1963 Jan 12;197:197–197. doi: 10.1038/197197a0. [DOI] [PubMed] [Google Scholar]
  12. Huston D. P., Rich R. R., Steinberg A. D., Truitt G. A. Requlation of cytotoxic lymphocyte responses in New Zealand mice by alloantigen-activated spleen cells. J Immunol. 1979 Apr;122(4):1476–1481. [PubMed] [Google Scholar]
  13. Kysela S., Steinberg A. D. Increased survival of NZB-W mice given multiple syngeneic young thymus grafts. Clin Immunol Immunopathol. 1973 Nov;2(1):133–136. doi: 10.1016/0090-1229(73)90043-3. [DOI] [PubMed] [Google Scholar]
  14. Ledbetter J. A., Rouse R. V., Micklem H. S., Herzenberg L. A. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med. 1980 Aug 1;152(2):280–295. doi: 10.1084/jem.152.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Loken M. R., Parks D. R., Herzenberg L. A. Two-color immunofluorescence using a fluorescence-activated cell sorter. J Histochem Cytochem. 1977 Jul;25(7):899–907. doi: 10.1177/25.7.330738. [DOI] [PubMed] [Google Scholar]
  16. Milich D. R., Gershwin M. E. The pathogenesis of autoimmunity in New Zealand mice. Semin Arthritis Rheum. 1980 Nov;10(2):111–147. doi: 10.1016/0049-0172(80)90004-9. [DOI] [PubMed] [Google Scholar]
  17. Miller M. H., Powell J. I., Sharrow S. O., Schultz A. R. Rapid data collection, analysis, and graphics for flow microfluorometry instrumentation. Rev Sci Instrum. 1978 Aug;49(8):1137–1142. doi: 10.1063/1.1135535. [DOI] [PubMed] [Google Scholar]
  18. Nakano T., Imai Y., Naiki M., Osawa T. Characterization of mouse helper and suppressor T cell subsets separated by lectins. J Immunol. 1980 Nov;125(5):1928–1932. [PubMed] [Google Scholar]
  19. Reisner Y., Linker-Israeli M., Sharon N. Separation of mouse thymocytes into two subpopulations by the use of peanut agglutinin. Cell Immunol. 1976 Jul;25(1):129–134. doi: 10.1016/0008-8749(76)90103-9. [DOI] [PubMed] [Google Scholar]
  20. Roelants G. E., London J., Mayor-Withey K. S., Serrano B. Peanut agglutinin. II. Characterization of the Thy-1, Tla and Ig phenotype of peanut agglutinin-positive cells in adult, embryonic and nude mice using double immunofluorescence. Eur J Immunol. 1979 Feb;9(2):139–145. doi: 10.1002/eji.1830090209. [DOI] [PubMed] [Google Scholar]
  21. Roubinian J. R., Papoian R., Pillarisetty R., Sawada S., Talal N. Immunological regulation of spontaneous antibodies to DNA and RNA. III. Early effects of neonatal thymectomy and splenectomy. Immunology. 1977 Sep;33(3):399–406. [PMC free article] [PubMed] [Google Scholar]
  22. Steinberg A. D., Law L. D., Talal N. The role of NZB-NZW F1 thymus in experimental tolerance and auto-immunity. Arthritis Rheum. 1970 Jul-Aug;13(4):369–377. doi: 10.1002/art.1780130402. [DOI] [PubMed] [Google Scholar]
  23. Steinberg A. D., Roths J. B., Murphy E. D., Steinberg R. T., Raveche E. S. Effects of thymectomy or androgen administration upon the autoimmune disease of MRL/Mp-lpr/lpr mice. J Immunol. 1980 Aug;125(2):871–873. [PubMed] [Google Scholar]
  24. Wagner H., Hardt C., Bartlett R., Röllinghoff M., Pfizenmaier K. Intrathymic differentiation of cytotoxic T lymphocyte (CTL) precursors. I. The CTL immunocompetence of peanut agglutinin-positive (cortical) and negative (medullary) Lyt 123 thymocytes. J Immunol. 1980 Dec;125(6):2532–2538. [PubMed] [Google Scholar]
  25. de Vries M. J., Hijmans W. Pathological changes of thymic epithelial cells and autoimmune disease in NZB, NZW and (NZB x NZW)F1 mice. Immunology. 1967 Feb;12(2):179–196. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES