Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1969 Jul 1;130(1):49–76. doi: 10.1084/jem.130.1.49

THE MECHANISM OF ACTION OF ANTI-LYMPHOCYTE SERUM

STUDIES OF ANTIBODY ELUATE

Eugene M Lance 1
PMCID: PMC2138667  PMID: 4183778

Abstract

Studies designed to gain insight into the mechanism of action of the active component of antilymphocyte serum were carried out using an antibody eluate prepared from the IgG fraction of anti-lymphocyte serum by absorption and subsequent elution from thymocyte membrane. The resulting antibody eluate was labeled with radionuclide tracer to determine the fate of the antibody in vivo. The result indicated that anti-lymphocytic antibodies are eliminated from recipients extremely rapidly. The mechanism for this rapid clearance appears to depend upon the absorption of antibody molecules onto lymphocyte surfaces and the subsequent clearing and degradation of the antibody-lymphocyte complexes by the reticuloendothelial system. Distribution studies confirm that the major site of antibody-lymphocyte interaction occurs in the periphery with relatively little penetration of antibody within lymphoid organs. Radioautographic studies showed that the pattern of localization within lymphoid and other organs is confined to rather specific areas. These observations are believed to offer strong support for the notion that anti-lymphocyte serum achieves its immunosuppressive effect by bringing about a selective ablation of the population of recirculating lymphocytes.

Full Text

The Full Text of this article is available as a PDF (2.2 MB).

Selected References

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

  1. BITENSKY L. CYTOTOXIC ACTION OF ANTIBODIES. Br Med Bull. 1963 Sep;19:241–244. doi: 10.1093/oxfordjournals.bmb.a070064. [DOI] [PubMed] [Google Scholar]
  2. Brent L., Courtenay T., Gowland G. Immunological reactivity of lymphoid cells after treatment with anti-lymphocytic serum. Nature. 1967 Sep 30;215(5109):1461–1464. doi: 10.1038/2151461a0. [DOI] [PubMed] [Google Scholar]
  3. Clark J. G., James K., Woodruff M. F. Elimination of normal horse IgG labelled with Iodine-131 in rats receiving horse anti-rat lymphocytic IgG. Nature. 1967 Aug 19;215(5103):869–870. doi: 10.1038/215869a0. [DOI] [PubMed] [Google Scholar]
  4. Denman A. M., Frenkel E. P. Mode of action of anti-lymphocyte globulin. I. The distribution of rabbit anti-lymphocyte globulin injected into rats and mice. Immunology. 1968 Jan;14(1):107–113. [PMC free article] [PubMed] [Google Scholar]
  5. Denman A. M., Frenkel E. P. Studies of the effect of induced immune lymphopenia. I. Enhanced effects of rabbit anti-rat lymphocyte globulin in rats tolerant to rabbit immunoglobulin G. J Immunol. 1967 Sep;99(3):498–507. [PubMed] [Google Scholar]
  6. EISEN H. N., PRESSMAN D. The zone of localization of antibodies VIII. Some properties of the antigen responsible for the renal localization of anti-kidney serum. J Immunol. 1950 Jun;64(6):487–498. [PubMed] [Google Scholar]
  7. GARVER R. M., COLE L. J. Passive transfer of bone marrow homotransplantation immunity with specific antisera. J Immunol. 1961 Mar;86:307–311. [PubMed] [Google Scholar]
  8. GORER P. A., AMOS D. B. Passive immunity in mice against C57BL leukosis E.L. 4 by means of iso-immune serum. Cancer Res. 1956 May;16(4):338–343. [PubMed] [Google Scholar]
  9. GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
  10. GRABAR P., WILLIAMS C. A. Méthode permettant l'étude conjuguée des proprietés électrophorétiques et immunochimiques d'un mélange de protéines; application au sérum sanguin. Biochim Biophys Acta. 1953 Jan;10(1):193–194. doi: 10.1016/0006-3002(53)90233-9. [DOI] [PubMed] [Google Scholar]
  11. Guttmann R. D., Carpenter C. B., Lindquist R. R., Merrill J. P. An immunosupressive site of action of heterologous antilymphocyte serum. Lancet. 1967 Feb 4;1(7484):248–249. doi: 10.1016/s0140-6736(67)91306-2. [DOI] [PubMed] [Google Scholar]
  12. Hintz B., Webber M. M. Antithymic antibody localization in the mouse. Nature. 1965 Nov 20;208(5012):797–798. doi: 10.1038/208797a0. [DOI] [PubMed] [Google Scholar]
  13. James K., Medawar P. B. Characterization of antilymphocytic antibody. Nature. 1967 Jun 3;214(5092):1052–1053. doi: 10.1038/2141052b0. [DOI] [PubMed] [Google Scholar]
  14. Jooste S. V. The effects of heterologous antilymphocytic antiserum in the late prenatal and early postnatal period in mice. Transplantation. 1968 Mar;6(2):277–286. doi: 10.1097/00007890-196803000-00012. [DOI] [PubMed] [Google Scholar]
  15. Lance E. M., Dresser D. W. Antigenicity in mice of antilymphocyte gamma-globulin. Nature. 1967 Jul 29;215(5100):488–490. doi: 10.1038/215488a0. [DOI] [PubMed] [Google Scholar]
  16. Levey R. H., Medawar P. B. Further experiments on the action of antilymphocytic antiserum. Proc Natl Acad Sci U S A. 1967 Aug;58(2):470–477. doi: 10.1073/pnas.58.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Levey R. H., Medawar P. B. Nature and mode of action of antilymphocytic antiserum. Proc Natl Acad Sci U S A. 1966 Oct;56(4):1130–1137. doi: 10.1073/pnas.56.4.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. SEHON A. H. PHYSICOCHEMICAL AND IMMUNOCHEMICAL METHODS FOR THE ISOLATION AND CHARACTERIZATION OF ANTIBODIES. Br Med Bull. 1963 Sep;19:183–191. doi: 10.1093/oxfordjournals.bmb.a070054. [DOI] [PubMed] [Google Scholar]
  19. Taub R. N., Lance E. M. Histopathological effects in mice of heterologous antilymphocyte serum. J Exp Med. 1968 Dec 1;128(6):1281–1307. doi: 10.1084/jem.128.6.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Turk J. L., Willoughby D. A. Central and peripheral effects of anti-lymphocyte sera. Lancet. 1967 Feb 4;1(7484):249–251. doi: 10.1016/s0140-6736(67)91307-4. [DOI] [PubMed] [Google Scholar]
  21. Unanue E. R., Dixon F. J. Experimental allergic glomerulonephritis induced in the rabbit with heterologous renal antigens. J Exp Med. 1967 Jan 1;125(1):149–162. doi: 10.1084/jem.125.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. WAKSMAN B. H., ARBOUYS S., ARNASON B. G. The use of specific "lymphocyte" antisera to inhibit hypersensitive reactions of the "delayed" type. J Exp Med. 1961 Dec 1;114:997–1022. doi: 10.1084/jem.114.6.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Woodruff M. F., Reid B. L., James K. Quantitative studies with antilymphocytic antibody. Nature. 1967 Nov 25;216(5117):758–762. doi: 10.1038/216758a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES