Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM

Ramsay Fuleihan*, Narayanaswamy Ramesh, Richard Loh, Haifa Jabara, Fred S. Rosen, Talal Chatila, Shu Man Fu, Ivan Stamenkovic, Raif S. Geha

*Corresponding author for this work

Research output: Contribution to journalArticle

328 Citations (Scopus)

Abstract

B lymphocytes from patients with X chromosome-linked immunoglobulin deficiency with normal or elevated serum IgM are unable to switch from the synthesis of IgM/IgD to that of other immunoglobulin isotypes. Isotype switch recombination was evaluated in three affected males by examining interleukin 4-driven IgE synthesis. T-cell-dependent IgE synthesis was completely absent in the B lymphocytes of the patients. In contrast, CD40 mAb plus interleukin 4 induced the patients' B cells to synthesize IgE and to undergo deletional switch recombination. Because interaction between CD40 and its ligand on activated T cells is critical for T-cell-driven isotype switching, we examined CD40 ligand expression. In contrast to normal T cells, lymphocytes from the patients expressed no detectable CD40 ligand on their surface after stimulation with phorbol 12-myristate 13-acetate and ionomycin, although the mRNA of the ligand was expressed normally. These results suggest that defective expression of the CD40 ligand underlies the failure of isotype switching in this disease.

Original languageEnglish (US)
Pages (from-to)2170-2173
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number6
DOIs
StatePublished - Jan 1 1993

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CD40 Ligand
X Chromosome
Immunoglobulin M
Immunoglobulins
Immunoglobulin E
Immunoglobulin Class Switching
T-Lymphocytes
B-Lymphocytes
Interleukin-4
Genetic Recombination
Immunoglobulin D
Ionomycin
Immunoglobulin Isotypes
Acetates
Lymphocytes
Ligands
Messenger RNA
Serum

Keywords

  • immunodeficiency
  • isotype switching
  • switch recombination

ASJC Scopus subject areas

  • General

Cite this

Fuleihan, Ramsay ; Ramesh, Narayanaswamy ; Loh, Richard ; Jabara, Haifa ; Rosen, Fred S. ; Chatila, Talal ; Fu, Shu Man ; Stamenkovic, Ivan ; Geha, Raif S. / Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 6. pp. 2170-2173.
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Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM. / Fuleihan, Ramsay; Ramesh, Narayanaswamy; Loh, Richard; Jabara, Haifa; Rosen, Fred S.; Chatila, Talal; Fu, Shu Man; Stamenkovic, Ivan; Geha, Raif S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 6, 01.01.1993, p. 2170-2173.

Research output: Contribution to journalArticle

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AU - Fuleihan, Ramsay

AU - Ramesh, Narayanaswamy

AU - Loh, Richard

AU - Jabara, Haifa

AU - Rosen, Fred S.

AU - Chatila, Talal

AU - Fu, Shu Man

AU - Stamenkovic, Ivan

AU - Geha, Raif S.

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N2 - B lymphocytes from patients with X chromosome-linked immunoglobulin deficiency with normal or elevated serum IgM are unable to switch from the synthesis of IgM/IgD to that of other immunoglobulin isotypes. Isotype switch recombination was evaluated in three affected males by examining interleukin 4-driven IgE synthesis. T-cell-dependent IgE synthesis was completely absent in the B lymphocytes of the patients. In contrast, CD40 mAb plus interleukin 4 induced the patients' B cells to synthesize IgE and to undergo deletional switch recombination. Because interaction between CD40 and its ligand on activated T cells is critical for T-cell-driven isotype switching, we examined CD40 ligand expression. In contrast to normal T cells, lymphocytes from the patients expressed no detectable CD40 ligand on their surface after stimulation with phorbol 12-myristate 13-acetate and ionomycin, although the mRNA of the ligand was expressed normally. These results suggest that defective expression of the CD40 ligand underlies the failure of isotype switching in this disease.

AB - B lymphocytes from patients with X chromosome-linked immunoglobulin deficiency with normal or elevated serum IgM are unable to switch from the synthesis of IgM/IgD to that of other immunoglobulin isotypes. Isotype switch recombination was evaluated in three affected males by examining interleukin 4-driven IgE synthesis. T-cell-dependent IgE synthesis was completely absent in the B lymphocytes of the patients. In contrast, CD40 mAb plus interleukin 4 induced the patients' B cells to synthesize IgE and to undergo deletional switch recombination. Because interaction between CD40 and its ligand on activated T cells is critical for T-cell-driven isotype switching, we examined CD40 ligand expression. In contrast to normal T cells, lymphocytes from the patients expressed no detectable CD40 ligand on their surface after stimulation with phorbol 12-myristate 13-acetate and ionomycin, although the mRNA of the ligand was expressed normally. These results suggest that defective expression of the CD40 ligand underlies the failure of isotype switching in this disease.

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