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Free access | 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, Newton Hyslop, Samih Alami, Fuad Farah, Eveline E. Schneeberger, and Fred S. Rosen

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114

Division of Allergy and Immunology, Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts 02114

Department of Pathology, Children's Hospital Medical Center, Boston, Massachusetts 02114

Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Department of Medicine, American University Medical Center, Beirut, Lebanon

Department of Pediatrics, American University Medical Center, Beirut, Lebanon

Find articles by Geha, R. in: PubMed | Google Scholar

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114

Division of Allergy and Immunology, Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts 02114

Department of Pathology, Children's Hospital Medical Center, Boston, Massachusetts 02114

Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Department of Medicine, American University Medical Center, Beirut, Lebanon

Department of Pediatrics, American University Medical Center, Beirut, Lebanon

Find articles by Hyslop, N. in: PubMed | Google Scholar

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114

Division of Allergy and Immunology, Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts 02114

Department of Pathology, Children's Hospital Medical Center, Boston, Massachusetts 02114

Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Department of Medicine, American University Medical Center, Beirut, Lebanon

Department of Pediatrics, American University Medical Center, Beirut, Lebanon

Find articles by Alami, S. in: PubMed | Google Scholar

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114

Division of Allergy and Immunology, Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts 02114

Department of Pathology, Children's Hospital Medical Center, Boston, Massachusetts 02114

Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Department of Medicine, American University Medical Center, Beirut, Lebanon

Department of Pediatrics, American University Medical Center, Beirut, Lebanon

Find articles by Farah, F. in: PubMed | Google Scholar

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114

Division of Allergy and Immunology, Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts 02114

Department of Pathology, Children's Hospital Medical Center, Boston, Massachusetts 02114

Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Department of Medicine, American University Medical Center, Beirut, Lebanon

Department of Pediatrics, American University Medical Center, Beirut, Lebanon

Find articles by Schneeberger, E. in: PubMed | Google Scholar

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114

Division of Allergy and Immunology, Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts 02114

Department of Pathology, Children's Hospital Medical Center, Boston, Massachusetts 02114

Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Department of Medicine, American University Medical Center, Beirut, Lebanon

Department of Pediatrics, American University Medical Center, Beirut, Lebanon

Find articles by Rosen, F. in: PubMed | Google Scholar

Published August 1, 1979 - More info

Published in Volume 64, Issue 2 on August 1, 1979
J Clin Invest. 1979;64(2):385–391. https://doi.org/10.1172/JCI109473.
© 1979 The American Society for Clinical Investigation
Published August 1, 1979 - Version history
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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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