Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Feb;71(2):531–535. doi: 10.1073/pnas.71.2.531

Immunoglobulin Synthesis In Vitro by Lymphocytes from Patients with Immune Deficiency: Requirement for a Special Serum Factor

P Wernet 1, F P Siegal 1, H Dickler 1, S Fu 1, H G Kunkel 1
PMCID: PMC388041  PMID: 4131278

Abstract

Certain patients with immune deficiency were encountered whose peripheral blood lymphocytes included no immunoglobulin-bearing cells. However, other markers of B type lymphocytes were observed; lymphocytes isolated free of macrophages showed the presence of receptors for the Fc fragment of IgG and for the third component of complement. One patient with a syndrome of thymoma and severe hypogammaglobulinemia was studied in special detail. In vitro the patient's cells were able to develop surface Ig in media supplemented with fetal-calf serum or normal human serum; in media supplemented with autologous serum, the cells developed no surface Ig. During culturing antigenic determinants of immunoglobulin became detectable in the medium, and both medium and cell-surface immunoglobulin underwent a shift from specific IgM determinants early in the culture period to IgG and IgA determinants later. Normal lymphocytes and thymocytes activated by concanavalin A repaired the deficiency in the patient's serum. These data support the concept that a factor possibly derived from T cells is missing from this patient's serum and that this factor is required for the maturation of the B cell for immunoglobulin synthesis.

A patient with X-linked agammaglobulinemia had a population of circulating lymphocytes with some surface characteristics that appeared similar to those of the B cells from the patient with thymoma. In contrast, however, no Ig synthesis by this patient's cultured cells could be demonstrated. The possible nature of the lymphocytes reacting with aggregated IgG in this case is discussed.

Keywords: B-cell markers, B-cell differentiation, serum factor, T-cell influence, mitogen action

Full text

PDF
531

Selected References

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

  1. Andersson J., Melchers F., Galanos C., Lüderitz O. The mitogenic effect of lipopolysaccharide on bone marrow-derived mouse lymphocytes. Lipid A as the mitogenic part of the molecule. J Exp Med. 1973 Apr 1;137(4):943–953. doi: 10.1084/jem.137.4.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baur S., Vitetta E. S., Sherr C. J., Schenkein I., Uhr J. W. Isolation of heavy and light chains of immunoglobulin from the surfaces of lymphoid cells. J Immunol. 1971 Apr;106(4):1133–1135. [PubMed] [Google Scholar]
  3. Bianco C., Patrick R., Nussenzweig V. A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization. J Exp Med. 1970 Oct 1;132(4):702–720. doi: 10.1084/jem.132.4.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Britton S. When allogeneic mouse spleen cells are mixed in vitro the T-cells secrete a product which guides the maturation of B-cells. Scand J Immunol. 1972;1(1):89–98. doi: 10.1111/j.1365-3083.1972.tb03738.x. [DOI] [PubMed] [Google Scholar]
  5. Bullock W. W., Möller E. "Spontaneous" B cell activation due to loss of normal mouse serum suppressor. Eur J Immunol. 1972 Dec;2(6):514–517. doi: 10.1002/eji.1830020609. [DOI] [PubMed] [Google Scholar]
  6. Byrd W. Restoration of the immune response to sheep erythrocytes by a serum factor. Nat New Biol. 1971 Jun 30;231(26):280–282. doi: 10.1038/newbio231280a0. [DOI] [PubMed] [Google Scholar]
  7. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  8. Cline M. J., Lehrer R. I. Phagocytosis by human monocytes. Blood. 1968 Sep;32(3):423–435. [PubMed] [Google Scholar]
  9. Dickler H. B., Kunkel H. G. Interaction of aggregated -globulin with B lymphocytes. J Exp Med. 1972 Jul 1;136(1):191–196. doi: 10.1084/jem.136.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gorczynski R. M., Miller R. G., Phillips R. A. Initiation of antibody production to sheep erythrocytes in vitro: replacement of the requirement for T-cells with a cell-free factor isolated from cultures of lymphoid cells. J Immunol. 1972 Feb;108(2):547–551. [PubMed] [Google Scholar]
  11. Hoffman M. K., Schmidt D., Oettgen H. F. Production of antibody to sheep red blood cells by human tonsil cells in vitro. Nature. 1973 Jun 15;243(5407):408–410. doi: 10.1038/243408a0. [DOI] [PubMed] [Google Scholar]
  12. MacLennan I. C. Antibody in the induction and inhibition of lymphocyte cytotoxicity. Transplant Rev. 1972;13:67–90. doi: 10.1111/j.1600-065x.1972.tb00060.x. [DOI] [PubMed] [Google Scholar]
  13. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Natvig J. B., Kunkel H. G. Detection of genetic antigens utilizing gamma globulins coupled to red blood cells. Nature. 1967 Jul 1;215(5096):68–69. doi: 10.1038/215068a0. [DOI] [PubMed] [Google Scholar]
  15. Perlmann P., Perlmann H., Wigzell H. Lymphocyte mediated cytotoxicity in vitro. Induction and inhibition by humoral antibody and nature of effector cells. Transplant Rev. 1972;13:91–114. doi: 10.1111/j.1600-065x.1972.tb00061.x. [DOI] [PubMed] [Google Scholar]
  16. Schimpl A., Wecker E. Stimulation of IgG antibody response in vitro by T cell-replacing factor. J Exp Med. 1973 Feb 1;137(2):547–552. doi: 10.1084/jem.137.2.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sjöberg O., Andersson J., Möller G. Reconstitution of the antibody response in vitro of T cell-deprived spleen cells by supernatants from spleen cell cultures. J Immunol. 1972 Dec;109(6):1379–1385. [PubMed] [Google Scholar]
  18. Watson J., Thoman M. A factor that can be used to regulate an in vitro primary immune response. Proc Natl Acad Sci U S A. 1972 Mar;69(3):594–598. doi: 10.1073/pnas.69.3.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zabriskie J. B., Lewshenia R., Möller G., Wehle B., Falk R. E. Lymphocytic responses to streptococcal antigens in glomerulonephritic patients. Science. 1970 May 29;168(3935):1105–1108. doi: 10.1126/science.168.3935.1105. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES