Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1971 May 1;133(5):1131–1148. doi: 10.1084/jem.133.5.1131

STUDIES ON THE LIFE HISTORY OF LYMPHOCYTES

I. THE LIFE-SPAN OF CELLS RESPONSIVE IN THE MIXED LYMPHOCYTE INTERACTION

Peter C Nowell 1, Darcy B Wilson 1
PMCID: PMC2138922  PMID: 5554100

Abstract

The life history, within the rat, of lymphocytes responsive to histocompatibility isoantigens in the mixed lymphocyte interaction was examined by the use of in vivo labeling with tritiated thymidine and radioautography. Lymphocytes in the peripheral blood and H-ARC (mitotic figures in the MLI) were compared with respect to the frequency of labeled cells and the median grain count. The following conclusions were drawn from this study: (a) Although some can be considered long-lived, the majority of H-ARC are the products of recent divisions in the body. (b) Adult thymectomy does not eliminate the production of long-lived lymphocytes, some of which are H-ARC. Hence, in addition to direct origin in the thymus, H-ARC, as well as other lymphocytes of the long-lived lymphocyte population, may derive from already existing thymus-derived cells in the circulation and thymus-dependent areas of the secondary lymphoid tissues. (c) Sublethal X-irradiation (600 R) in combination with adult thymectomy does not eliminate the capacity to produce some long-lived lymphocytes, however, few if any are H-ARC. (d) H-ARC and other long-lived lymphocytes appear to go through a series of rapid multiple divisions before they enter the circulation. Thereafter, long-lived lymphocytes appear to undergo intermittent single divisions which decrease both the frequency and median grain count of labeled cells gradually with time. On the other hand, labeled H-ARC maintain a more stable grain count despite a rapid decrease in frequency with time. This is taken to indicate that H-ARC are less likely to undergo occasional single divisions during their life-span, but may undergo periodic rapid sequential divisions. A speculative model is developed from these data on the life history of H-ARC which may be of predictive value in future studies and which can be tested against known facts.

Full Text

The Full Text of this article is available as a PDF (928.4 KB).

Selected References

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

  1. Gowans J. L., Uhr J. W. The carriage of immunological memory by small lymphocytes in the rat. J Exp Med. 1966 Nov 1;124(5):1017–1030. doi: 10.1084/jem.124.5.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. MOORHEAD P. S., NOWELL P. C., MELLMAN W. J., BATTIPS D. M., HUNGERFORD D. A. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res. 1960 Sep;20:613–616. doi: 10.1016/0014-4827(60)90138-5. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Miller J. F., Osoba D. Current concepts of the immunological function of the thymus. Physiol Rev. 1967 Jul;47(3):437–520. doi: 10.1152/physrev.1967.47.3.437. [DOI] [PubMed] [Google Scholar]
  5. Nowell P. C., Hirsch B. E., Fox D. H., Wilson D. B. Evidence for the existence of multipotential lympho-hematopoietic stem cells in adult rat. J Cell Physiol. 1970 Apr;75(2):151–158. doi: 10.1002/jcp.1040750203. [DOI] [PubMed] [Google Scholar]
  6. Simons M. J., Fowler R. Chorioallantoic membrane lesions produced by inoculation of adult fowl small lymphocytes. Nature. 1966 Feb 5;209(5023):588–589. doi: 10.1038/209588a0. [DOI] [PubMed] [Google Scholar]
  7. Wilson D. B., Blyth JL NOWELL P. C. Quantitative studies on the mixed lymphocyte interaction in rats. 3. Kinetics of the response. J Exp Med. 1968 Nov 1;128(5):1157–1181. doi: 10.1084/jem.128.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Wilson D. B., Nowell P. C. Quantitative studies on the mixed lymphocyte interaction in rats. IV. Immunologic potentiality of the responding cells. J Exp Med. 1970 Feb;131(2):391–407. doi: 10.1084/jem.131.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Wilson D. B., Nowell P. C. Quantitative studies on the mixed lymphocyte interaction in rats. V. Tempo and specificity of the proliferative response and the number of reactive cells from immunized donors. J Exp Med. 1971 Mar 1;133(3):442–453. doi: 10.1084/jem.133.3.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Wilson D. B. Quantitative studies on the mixed lymphocyte interaction in rats. I. Conditions and parameters of response. J Exp Med. 1967 Oct 1;126(4):625–654. doi: 10.1084/jem.126.4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Wilson D. B., Silvers W. K., Nowell P. C. Quantitative studies on the mixed lymphocyte interaction in rats. II. Relationship of the proliferative response to the immunologic status of the donors. J Exp Med. 1967 Oct 1;126(4):655–665. doi: 10.1084/jem.126.4.655. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES