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. 1968 Sep 1;128(3):437–457. doi: 10.1084/jem.128.3.437

CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

I. SEPARATE SPLENIC ANTIGEN-SENSITIVE UNITS FOR DIFFERENT TYPES OF ANTI-SHEEP ANTIBODY-FORMING CELLS

G M Shearer 1, G Cudkowicz 1, Mary St James Connell 1, R L Priore 1
PMCID: PMC2138534  PMID: 5666959

Abstract

Spleen cell suspensions of unprimed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice. In the presence of antigen (sheep erythrocytes) these precursors, called antigen-sensitive units, gave rise to progeny cells secreting specific antibody. We studied quantitatively the production of cells releasing IgM hemolysins (direct plaque-forming cells), IgG hemolysins (indirect plaque-forming cells), and hemagglutinins (cluster-forming cells). We found that each of these immunocyte populations was distinct, i.e., that cells releasing agglutinins did not, as a rule, release hemolysins, and vice versa. We also found that cell populations secreting IgM hemolysins did not shift, under certain experimental conditions, to the production of IgG hemolysins during the primary immune response. By transplanting graded numbers of spleen cells, we succeeded in limiting to one or a few the number of antigen-sensitive units that reached the recipient spleen. We estimated thereby the frequency of antigen-sensitive units in donor cell suspensions and tested their potential for production of immunocytes of more than one type. Our results indicated that antigen-sensitive units were unipotent for they displayed in the spleens of unprimed donors the same restrictions of function and heterogeneity (antibody-specificity differentiation, antibody-class differentiation) found among antibody-forming cells. Furthermore, antigen-sensitive precursors for direct plaque-forming cells, indirect plaque-forming cells, and cluster-forming cells were detected in the spleens of unprimed mice in different frequencies, i.e., 1 in ∼ 106, 1 in ∼ 7 x 106, and 1 in ∼ 19 x 106 spleen cells, respectively. We concluded that relatively advanced differentiation of potentially competent cells occurs before sheep erythrocyte administration. The relevance of this finding for the broad spectrum of immunologic reactivities and for the heterogeneity of antibody responses to given antigens was discussed.

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Selected References

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

  1. BORAKER D. K., HILDEMANN W. H. MATURATION OF ALLOIMMUNE RESPONSIVENESS IN MICE. Transplantation. 1965 Mar;3:202–223. doi: 10.1097/00007890-196503000-00008. [DOI] [PubMed] [Google Scholar]
  2. Biozzi G., Stiffel C., Mouton D., Liacopoulosbriot M., Decreusefond C., Bouthillier Y. Etude du phénomène de l'immuno-cyto-adhérence au cours de l'immunisation. Ann Inst Pasteur (Paris) 1966 Mar;110(3 Suppl):7–32. [PubMed] [Google Scholar]
  3. Bosma M. J., Makinodan T., Walburg H. E., Jr Development of immunologic competence in germfree and conventional mice. J Immunol. 1967 Aug;99(2):420–430. [PubMed] [Google Scholar]
  4. Brown R. A., Makinodan T., Albright J. F. Significance of a single-hit event in the initiation of antibody response. Nature. 1966 Jun 25;210(5043):1383–1384. doi: 10.1038/2101383a0. [DOI] [PubMed] [Google Scholar]
  5. Celada F., Wigzell H. Immune responses in spleen colonies. II. Clonal assortment of 19S- and 7S-producing cells in mice reacting against two antigens. Immunology. 1966 Nov;11(5):453–466. [PMC free article] [PubMed] [Google Scholar]
  6. Claman H. N., Chaperon E. A., Triplett R. F. Immunocompetence of transferred thymus-marrow cell combinations. J Immunol. 1966 Dec;97(6):828–832. [PubMed] [Google Scholar]
  7. Doria G., Agarossi G. The effect of thymic action on the precursors of antigen-sensitive cells. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1366–1372. doi: 10.1073/pnas.58.4.1366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dresser D. W., Wortis D. H. Use of an antiglobulin serum to detect cells producing antibody with low haemolytic efficiency. Nature. 1965 Nov 27;208(5013):859–861. doi: 10.1038/208859a0. [DOI] [PubMed] [Google Scholar]
  9. FRIEDMAN H. DISTRIBUTION OF ANTIBODY PLAQUE FORMING CELLS IN VARIOUS TISSUES OF SEVERAL STRAINS OF MICE INJECTED WITH SHEEP ERYTHROCYTES. Proc Soc Exp Biol Med. 1964 Nov;117:526–530. doi: 10.3181/00379727-117-29628. [DOI] [PubMed] [Google Scholar]
  10. Kennedy J. C., Till J. E., Siminovitch L., McCulloch E. A. The proliferative capacity of antigen-sensitive precursors of hemolytic plaque-forming cells. J Immunol. 1966 Jun;96(6):973–980. [PubMed] [Google Scholar]
  11. Mitchell G. F., Miller J. F. Immunological activity of thymus and thoracic-duct lymphocytes. Proc Natl Acad Sci U S A. 1968 Jan;59(1):296–303. doi: 10.1073/pnas.59.1.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. NOSSAL G. J., SZENBERG A., ADA G. L., AUSTIN C. M. SINGLE CELL STUDIES ON 19S ANTIBODY PRODUCTION. J Exp Med. 1964 Mar 1;119:485–502. doi: 10.1084/jem.119.3.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. NUSSENZWEIG R. S., MERRYMAN C., BENACERRAF B. ELECTROPHORETIC SEPARATION AND PROPERTIES OF MOUSE ANTIHAPTEN ANTIBODIES INVOLVED IN PASSIVE CUTANEOUS ANAPHYLAXIS AND PASSIVE HEMOLYSIS. J Exp Med. 1964 Aug 1;120:315–328. doi: 10.1084/jem.120.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nakano M., Braun W. Fluctuation tests with antibody-forming spleen cell populations. Science. 1966 Jan 21;151(3708):338–340. doi: 10.1126/science.151.3708.338. [DOI] [PubMed] [Google Scholar]
  15. Nettesheim P., Makinodan T., Williams M. L. Regenerative potential of immunocompetent cells. I. Lack of recovery of secondary antibody-forming potential after x-irradiation. J Immunol. 1967 Jul;99(1):150–157. [PubMed] [Google Scholar]
  16. Osoba D. Thymic control of cellular differentiation in the immunological system. Proc Soc Exp Biol Med. 1968 Feb;127(2):418–420. doi: 10.3181/00379727-127-32705. [DOI] [PubMed] [Google Scholar]
  17. Pernis B., Chiappino G., Kelus A. S., Gell P. G. Cellular localization of immunoglobulins with different allotypic specificities in rabbit lymphoid tissues. J Exp Med. 1965 Nov 1;122(5):853–876. doi: 10.1084/jem.122.5.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pinchuck P., Fishman M., Adler F. L., Maurer P. H. Antibody formation: initiation in "nonresponder" mice by macrophage synthetic polypeptide RNA. Science. 1968 Apr 12;160(3824):194–195. doi: 10.1126/science.160.3824.194. [DOI] [PubMed] [Google Scholar]
  19. Playfair J. H., Papermaster B. W., Cole L. J. Focal antibody production by transferred spleen cells in irradiated mice. Science. 1965 Aug 27;149(3687):998–1000. doi: 10.1126/science.149.3687.998. [DOI] [PubMed] [Google Scholar]
  20. Soothill J. F., Hayes K., Dudgeon J. A. The immunoglobulins in congenital rubella. Lancet. 1966 Jun 25;1(7452):1385–1388. doi: 10.1016/s0140-6736(66)90299-6. [DOI] [PubMed] [Google Scholar]
  21. Sterzl J., Ríha I. Detection of cells producing 7S antibodies by the plaque technique. Nature. 1965 Nov 27;208(5013):858–859. doi: 10.1038/208858a0. [DOI] [PubMed] [Google Scholar]
  22. Takeya K., Nomoto K. Characteristics of antibody response in young or thymectomized mice. J Immunol. 1967 Oct;99(4):831–836. [PubMed] [Google Scholar]
  23. Trentin J., Wolf N., Cheng V., Fahlberg W., Weiss D., Bonhag R. Antibody production by mice repopulated with limited numbers of clones of lymphoid cell precursors. J Immunol. 1967 Jun;98(6):1326–1337. [PubMed] [Google Scholar]
  24. UHR J. W., FINKELSTEIN M. S. Antibody formation. IV. Formation of rapidly and slowly sedimenting antibodies and immunological memory to bacteriophage phi-X 174. J Exp Med. 1963 Mar 1;117:457–477. doi: 10.1084/jem.117.3.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Voisin G. A., Kinsky R. G., Jansen F. K. Transplantation immunity: localization in mouse serum of antibodies responsible for haemagglutination, cytotoxicity and enhancement. Nature. 1966 Apr 9;210(5032):138–139. doi: 10.1038/210138a0. [DOI] [PubMed] [Google Scholar]
  26. Weiler E. Differential activity of allelic gamma-globulin genes in antibody-producing cells. Proc Natl Acad Sci U S A. 1965 Dec;54(6):1765–1772. doi: 10.1073/pnas.54.6.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Weiler E., Melletz E. W., Breuninger-Peck E. Facilitation of immune hemolysis by an interaction between red cell-sensitizing antibody and gamma-globulin allotype antibody. Proc Natl Acad Sci U S A. 1965 Nov;54(5):1310–1317. doi: 10.1073/pnas.54.5.1310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wolf N. S., Trentin J. J. Hemopoietic colony studies. V. Effect of hemopoietic organ stroma on differentiation of pluripotent stem cells. J Exp Med. 1968 Jan 1;127(1):205–214. doi: 10.1084/jem.127.1.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wortis H. H., Taylor R. B., Dresser D. W. Antibody production studied by means of the LHG assay. I. The splenic response of CBA mice to sheep erythrocytes. Immunology. 1966 Dec;11(6):603–616. [PMC free article] [PubMed] [Google Scholar]
  30. Zaalberg O. B., van der Meul V. A., van Twisk J. M. Antibody production by single spleen cells: a comparative study of the cluster and agar-plaque formation. Nature. 1966 Apr 30;210(5035):544–545. doi: 10.1038/210544a0. [DOI] [PubMed] [Google Scholar]
  31. Zaalberg O. B., van der Meul V. A., van Twisk M. J. Antibody production by isolated spleen cells: a study of the cluster and the plaque techniques. J Immunol. 1968 Feb;100(2):451–458. [PubMed] [Google Scholar]

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