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. 1966 Jul;11(1):19–27.

The formation of immunoglobulins by human tissues in vitro

III. Spleen, lymph nodes, bone marrow and thymus

R Van Furth, Henrica R E Schuit, W Hijmans
PMCID: PMC1423753  PMID: 4161983

Abstract

The site of immunoglobulin formation in human tissues was studied with three techniques: incubation of tissue fragments with radioactive amino acids followed by autoradiographic analysis of the synthesized immunoglobulins, immunofluorescent staining of tissue sections and cell suspensions, and morphological examination.

These studies showed that the spleen, lymph nodes and bone marrow synthesize IgG, IgA and IgM. In agammaglobulinaemia, one bone marrow sample showed no immunoglobulin synthesis, the other sample synthesized a trace of IgG. Immunofluorescent staining has demonstrated that in the spleen and lymph nodes plasma cells and large and medium-sized lymphocytes were positive for IgG, IgA or IgM; small lymphocytes were only positive for IgM. In bone-marrow samples, however, only plasma cells were positive for immunoglobulins. It is discussed whether in the bone marrow the cells that synthesize immunoglobulins do not originate in this organ, but derive from other lymphopoietic organs.

The normal thymus showed a different pattern because it synthesized only IgG and IgA. The plasma cells and medium-sized lymphocytes, which synthesize immunoglobulins, were localized predominantly in the interstitial connective tissue and ocasionally in the medulla, both near blood vessels. In all likelihood these cells did not originate in the thymus, but were trapped in this organ from the circulation. In autoimmune diseases, however, the thymus showed IgM-positive germinal centres and plasma cells and synthesized IgG, IgA and also IgM.

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Selected References

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  1. ASKONAS B. A., WHITE R. G. Sites of antibody production in the guinea-pig; the relation between in vitro synthesis of anti-ovalbumin and gamma-globulin and distribution of antibody-containing plasma cells. Br J Exp Pathol. 1956 Feb;37(1):61–74. [PMC free article] [PubMed] [Google Scholar]
  2. BALFOUR B. M., COOPER E. H., ALPEN E. L. MORPHOLOGICAL AND KINETIC STUDIES ON ANTIBODY-PRODUCING CELLS IN RAT LYMPH NODES. Immunology. 1965 Mar;8:230–244. [PMC free article] [PubMed] [Google Scholar]
  3. BANEY R. N., VAZQUEZ J. J., DIXON F. J. Cellular proliferation in relation to antibody synthesis. Proc Soc Exp Biol Med. 1962 Jan;109:1–4. doi: 10.3181/00379727-109-27083. [DOI] [PubMed] [Google Scholar]
  4. BAUER D. C., MATHIES M. J., STAVITSKY A. B. Sequences of synthesis of gamma-1 macroglobulin and gamma-2 globulin antibodies during primary and secondary responses to proteins, salmonella antigens, and phage. J Exp Med. 1963 Jun 1;117:889–907. doi: 10.1084/jem.117.6.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BURNET F. M., HOLMES M. C. Immunological function of thymus and bursa of Fabricius. Thymus lesions in an auto-immune disease of mice. Nature. 1962 Apr 14;194:146–147. doi: 10.1038/194146a0. [DOI] [PubMed] [Google Scholar]
  6. BURNET F. M., MACKAY I. R. Lymphoepithelial structures and autoimmune disease. Lancet. 1962 Nov 17;2(7264):1030–1033. doi: 10.1016/s0140-6736(62)92710-1. [DOI] [PubMed] [Google Scholar]
  7. CHIAPPINO G., PERNIS B. DEMONSTRATION WITH IMMUNOFLUORESCENCE OF 19S MACROGLOBULINS AND 7S GAMMA GLOBULINS IN DIFFERENT CELLS OF THE HUMAN SPLEEN. Pathol Microbiol (Basel) 1964;27:8–15. doi: 10.1159/000161448. [DOI] [PubMed] [Google Scholar]
  8. CLARK S. L., Jr The thymus in mice of strain 129/J, studied with the electron microscope. Am J Anat. 1963 Jan;112:1–33. doi: 10.1002/aja.1001120102. [DOI] [PubMed] [Google Scholar]
  9. COONS A. H., LEDUC E. H., CONNOLLY J. M. Studies on antibody production. I. A method for the histochemical demonstration of specific antibody and its application to a study of the hyperimmune rabbit. J Exp Med. 1955 Jul 1;102(1):49–60. doi: 10.1084/jem.102.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. CRUCHAUD A., ROSEN F. S., CRAIG J. M., JANEWAY C. A., GITLIN D. The site of synthesis of the 19S gamma-globulins in dysgammaglobulinemia. J Exp Med. 1962 Jun 1;115:1141–1148. doi: 10.1084/jem.115.6.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DIXON F. J., WEIGLE W. O., ROBERTS J. C. Comparison of antibody responses associated with the transfer of rabbit lymph-node, peritoneal exudate, and thymus cells. J Immunol. 1957 Jan;78(1):56–62. [PubMed] [Google Scholar]
  12. 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]
  13. GENGOZIAN N., MAKINODAN T., SHEKARCHI I. C. Transplantation of antibody-forming cells in lethally irradiated mice. J Immunol. 1961 Feb;86:113–122. [PubMed] [Google Scholar]
  14. HOLMES M. C., GORIE J., BURNET F. M. Transmission by splenic cells of an autoimmune disease occurring spontaneously in mice. Lancet. 1961 Sep 16;2(7203):638–639. doi: 10.1016/s0140-6736(61)90313-0. [DOI] [PubMed] [Google Scholar]
  15. HUTCHINS G. M., HARVEY A. M. THE THYMUS IN SYSTEMIC LUPUS ERYTHEMATOSUS. Bull Johns Hopkins Hosp. 1964 Nov;115:355–378. [PubMed] [Google Scholar]
  16. LANGEVOORT H. L. The histophysiology of the antibody response. I. Histogenesis of the plasma cell reaction in rabbit spleen. Lab Invest. 1963 Jan;12:106–118. [PubMed] [Google Scholar]
  17. LEDUC E. H., COONS A. H., CONNOLLY J. M. Studies on antibody production. II. The primary and secondary responses in the popliteal lymph node of the rabbit. J Exp Med. 1955 Jul 1;102(1):61–72. doi: 10.1084/jem.102.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MACKAY I. R., DEGAIL P. THYMIC "GERMINAL CENTRES" AND PLASMA CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS. Lancet. 1963 Sep 28;2(7309):667–667. doi: 10.1016/s0140-6736(63)90458-6. [DOI] [PubMed] [Google Scholar]
  19. MARSHALL A. H., WHITE R. G. The immunological reactivity of the thymus. Br J Exp Pathol. 1961 Aug;42:379–385. [PMC free article] [PubMed] [Google Scholar]
  20. MELLORS R. C., KORNGOLD L. THE CELLULAR ORIGIN OF HUMAN IMMUNOGLOBULINS (GAMMA-2, GAMMA-1M, GAMMA-1A). J Exp Med. 1963 Sep 1;118:387–396. doi: 10.1084/jem.118.3.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. ORTEGA L. G., MELLORS R. C. Cellular sites of formation of gamma globulin. J Exp Med. 1957 Nov 1;106(5):627–640. doi: 10.1084/jem.106.5.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. STONER R. D., BOND V. P. ANTIBODY FORMATION BY TRANSPLANTED BONE MARROW, SPLEEN, LYMPH NODES AND THYMUS CELLS IN IRRADIATED RECIPIENTS. J Immunol. 1963 Aug;91:185–196. [PubMed] [Google Scholar]
  23. STONER R. D., HALE W. M. Antibody production by thymus and Peyer's patches intraocular transplants. J Immunol. 1955 Sep;75(3):203–208. [PubMed] [Google Scholar]
  24. THORBECKE G. J., ASOFSKY R. M., HOCHWALD G. M., SISKIND G. W. Gamma globulin and antibody formation in vitro. III. Induction of secondary response at different intervals after the primary; the role of secondary nodules in the preparation for the secondary response. J Exp Med. 1962 Sep 1;116:295–310. doi: 10.1084/jem.116.3.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. THORBECKE G. J., BENACERRAF B. The reticulo-endothelial system and immunological phenomena. Prog Allergy. 1962;6:559–598. [PubMed] [Google Scholar]
  26. THORBECKE G. J. Gamma globulin and antibody formation in vitro. I. Gamma globulin formation in tissues from immature and normal adult rabbits. J Exp Med. 1960 Aug 1;112:279–292. doi: 10.1084/jem.112.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. THORBECKE G. J., KEUNING F. J. Antibody and gamma globulin formation in vitro in hemopoietic organs. J Infect Dis. 1956 Mar-Apr;98(2):157–171. doi: 10.1093/infdis/98.2.157. [DOI] [PubMed] [Google Scholar]
  28. THORBECKE G. J., KEUNING F. J. Antibody formation in vitro by haemopoietic organs after subcutaneous and intravenous immunization. J Immunol. 1953 Feb;70(2):129–134. [PubMed] [Google Scholar]
  29. VAZQUEZ J. J. Antibody- or gamma globulin--forming cells, as observed by the fluorescent antibody technic. Lab Invest. 1961 Nov-Dec;10:1110–1125. [PubMed] [Google Scholar]
  30. VOS O., DE VRIES M. J., COLLENTEUR J. C., VAN BEKKUM D. W. Transplantation of homologous and heterologous lymphoid cells in x-irradiated and non-irradiated mice. J Natl Cancer Inst. 1959 Jul;23(1):53–73. [PubMed] [Google Scholar]
  31. WEISS L. Electron microscopic, observations on the vascular barrier in the cortex of the thymus of the mouse. Anat Rec. 1963 Mar;145:413–437. doi: 10.1002/ar.1091450306. [DOI] [PubMed] [Google Scholar]
  32. WHITE R. G., COONS A. H., CONNOLLY J. M. Studies on antibody production. III. The alum granuloma. J Exp Med. 1955 Jul 1;102(1):73–82. doi: 10.1084/jem.102.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. WHITE R. G., MARSHALL A. H. The autoimmune response in myasthenia gravis. Lancet. 1962 Jul 21;2(7247):120–123. doi: 10.1016/s0140-6736(62)90005-3. [DOI] [PubMed] [Google Scholar]
  34. van Furth R., Schuit H. R., Hijmans W. The formation of immunoglobulins by human tissues in vitro. IV. Circulating lymphocytes in normal and pathological conditions. Immunology. 1966 Jul;11(1):29–40. [PMC free article] [PubMed] [Google Scholar]
  35. van Furth R., Schuit R. E., Hijmans W. The formation of immunoglobulins by human tissues in vitro. I. The methods and their specificity. Immunology. 1966 Jul;11(1):1–11. [PMC free article] [PubMed] [Google Scholar]
  36. van Furth R. The formation of immunoglobulins by human tissues in vitro. II. Quantitative studies. Immunology. 1966 Jul;11(1):13–18. [PMC free article] [PubMed] [Google Scholar]

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