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. 1979 Aug;64(2):385–391. doi: 10.1172/JCI109473

Hyper Immunoglobulin M Immunodeficiency (Dysgammaglobulinemia)

PRESENCE OF IMMUNOGLOBULIN M-SECRETING PLASMACYTOID CELLS IN PERIPHERAL BLOOD AND FAILURE OF IMMUNOGLOBULIN M-IMMUNOGLOBULIN G SWITCH IN B-CELL DIFFERENTIATION

Raif S Geha 1,2,3,4,5,6,7,8, Newton Hyslop 1,2,3,4,5,6,7,8, Samih Alami 1,2,3,4,5,6,7,8, Fuad Farah 1,2,3,4,5,6,7,8, Eveline E Schneeberger 1,2,3,4,5,6,7,8, Fred S Rosen 1,2,3,4,5,6,7,8
PMCID: PMC372130  PMID: 313404

Abstract

The peripheral blood lymphocytes of nine patients with hyper immunoglobulin (Ig)M immunodeficiency were studied in an attempt to define the cellular basis of this disorder. B cells were normal in number but qualitatively abnormal in all patients. Approximately one-half of the B cell consisted of small lymphocytes (7-9 μm in diameter) bearing surface IgM and IgD, as well as C3 receptors. These cells were driven to secrete IgM but not IgG after in vitro stimulation by pokeweed mitogen. In the blood there were also large lymphocytes (10-14 μm in diameter) that possessed surface as well as intracytoplasmic IgM but lacked C3 receptors. These cells spontaneously secreted large amounts of IgM in vitro and on electron microscopy were found to be rich in rough endoplasmic reticulum. Such a subpopulation of lymphoid cells was not detected in normal peripheral blood and was unique for all patients with hyper IgM immunodeficiency studied.

T cells from all patients were normal in number and in function both in vivo and in vitro and were able to generate adequate T-cell help to support IgG synthesis by normal B cells. No evidence was obtained for T cells capable of suppressing normal IgG synthesis in any of the patients after coculture with normal peripheral blood lymphocytes. The defect in hyper IgM immunodeficiency is intrinsic to B cells, which fail to switch from IgM to IgG synthesis.

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Selected References

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

  1. Blaese R. M., Weiden P. L., Koski I., Dooley N. Infectious agammaglobulinemia: transmission of immunodeficiency with grafts of agammaglobulinemic cells. J Exp Med. 1974 Oct 1;140(4):1097–1101. doi: 10.1084/jem.140.4.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Geha R. S., Merler E. Response of human thymus-derived (T) and non-thymus-derived (B) lymphocytes to mitogenic stimulation in vitro. Eur J Immunol. 1974 Mar;4(3):193–199. doi: 10.1002/eji.1830040308. [DOI] [PubMed] [Google Scholar]
  4. Geha R. S., Rosen F. S., Merler E. Identification and characterization of subpopulations of lymphocytes in human peripheral blood after fractionation on discontinuous gradients of albumin. The cellular defect in X-linked agammaglobulinemia. J Clin Invest. 1973 Jul;52(7):1726–1734. doi: 10.1172/JCI107354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Geha R. S., Schneeberger E., Rosen F. S., Merler E. Interaction of human thymus-derived and non-thymus-derived lymphocytes in vitro. Induction of proliferation and antibody synthesis in B lymphocytes by a soluble factor released from antigen-stimulated T lymphocytes. J Exp Med. 1973 Nov 1;138(5):1230–1247. doi: 10.1084/jem.138.5.1230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldman A. S., Ritzmann S. E., Houston E. W., Sidwell S., Bratcher R., Levin W. C. Dysgammaglobulinemic antibody deficiency syndrome. J Pediatr. 1967 Jan;70(1):16–27. doi: 10.1016/s0022-3476(67)80161-6. [DOI] [PubMed] [Google Scholar]
  7. HINZ C. F., BOYER J. T. DYSGAMMAGLOBULINEMIA IN THE ADULT MANIFESTED AS AUTOIMMUNE HEMOLYTIC ANEMIA. SEROLOGIC AND IMMUNOCHEMICAL CHARACTERIZATION OF AN ANTIBODY OF UNUSUAL SPECIFICITY. N Engl J Med. 1963 Dec 19;269:1329–1335. doi: 10.1056/NEJM196312192692501. [DOI] [PubMed] [Google Scholar]
  8. Hobbs J. R., Russell A., Worlledge S. M. Dysgammaglobulinaemia type IV C. Clin Exp Immunol. 1967 Sep;2(5):589–599. [PMC free article] [PubMed] [Google Scholar]
  9. Lawton A. R., 3rd, Asofsky R., Hylton M. B., Cooper M. D. Suppression of immunoglobulin class synthesis in mice. I. Effects of treatment with antibody to -chain. J Exp Med. 1972 Feb 1;135(2):277–297. doi: 10.1084/jem.135.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nilsson K., Klein G., Henle W., Henle G. The establishment of lymphoblastoid lines from adult and fetal human lymphoid tissue and its dependence on EBV. Int J Cancer. 1971 Nov 15;8(3):443–450. doi: 10.1002/ijc.2910080312. [DOI] [PubMed] [Google Scholar]
  11. Press J. L., Klinman N. R., McDevitt H. O. Expression of Ia antigens on hapten-specific B cells. I. Delineation of B-cell subpopulations. J Exp Med. 1976 Aug 1;144(2):414–427. doi: 10.1084/jem.144.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rosen F. S., Janeway C. A. The gamma globulins. 3. The antibody deficiency syndromes. N Engl J Med. 1966 Sep 29;275(13):709–contd. doi: 10.1056/NEJM196609292751307. [DOI] [PubMed] [Google Scholar]
  13. TERASAKI P. I., MCCLELLAND J. D. MICRODROPLET ASSAY OF HUMAN SERUM CYTOTOXINS. Nature. 1964 Dec 5;204:998–1000. doi: 10.1038/204998b0. [DOI] [PubMed] [Google Scholar]
  14. Van Alten P. J., Cain W. A., Good R. A., Cooper M. D. Gamma globulin production and antibody synthesis in chickens bursectomized as embryos. Nature. 1968 Jan 27;217(5126):358–360. doi: 10.1038/217358a0. [DOI] [PubMed] [Google Scholar]
  15. Vitetta E. S., Uhr J. W. Immunoglobulin-receptors revisited. Science. 1975 Sep 19;189(4207):964–969. doi: 10.1126/science.1083069. [DOI] [PubMed] [Google Scholar]
  16. Waldmann T. A., Durm M., Broder S., Blackman M., Blaese R. M., Strober W. Role of suppressor T cells in pathogenesis of common variable hypogammaglobulinaemia. Lancet. 1974 Sep 14;2(7881):609–613. doi: 10.1016/s0140-6736(74)91940-0. [DOI] [PubMed] [Google Scholar]

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