A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcγRIIb alters receptor expression and associates with autoimmunity. II. Differential binding of GATA4 and Yin-Yang1 transcription factors and correlated receptor expression and function

Kaihong Su, Xiaoli Li, Jeffrey C. Edberg, Jianming Wu, Polly Ferguson, Robert P. Kimberly

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Abstract

The immunoreceptor tyrosine-based inhibitory motif-containing FcγRIIb modulates immune function on multiple cell types including B cells, monocytes/macrophages, and dendritic cells. The promoter for the human FCGR2B is polymorphic, and the less frequent 2B.4 promoter haplotype is associated with the autoimmune phenotype of systemic lupus erythematosus. In the present study, we demonstrate that the 2B.4 promoter haplotype of FCGR2B has increased binding capacity for GATA4 and Yin-Yang1 (YY1) transcription factors in both B lymphocytes and monocytes, and that overexpression of GATA4 or YY1 enhances the FCGR2B promoter activity. The 2B.4 haplotype leads to elevated expression of the endogenous receptor in heterozygous donors by ≈1.5-fold as assessed on EBV-transformed cells, primary B lymphocytes, and CD14+ monocytes. This increased expression accentuates the inhibitory effect of FcγRIIb on B cell Ag receptor signaling, measured by Ca2+ influx and cell viability in B cells. Our results indicate that transcription factors GATA4 and YY1 are involved in the regulation of FcγRIIb expression, and that the expression variants of FcγRIIb lead to altered cell signaling, which may contribute to autoimmune pathogenesis in humans.

Original languageEnglish (US)
Pages (from-to)7192-7199
Number of pages8
JournalJournal of Immunology
Volume172
Issue number11
StatePublished - Jun 1 2004

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Autoimmunity
Haplotypes
Tyrosine
B-Lymphocytes
Transcription Factors
Monocytes
GATA4 Transcription Factor
Human Herpesvirus 4
Systemic Lupus Erythematosus
Dendritic Cells
Cell Survival
Macrophages
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcγRIIb alters receptor expression and associates with autoimmunity. II. Differential binding of GATA4 and Yin-Yang1 transcription factors and correlated receptor expression and function",
abstract = "The immunoreceptor tyrosine-based inhibitory motif-containing FcγRIIb modulates immune function on multiple cell types including B cells, monocytes/macrophages, and dendritic cells. The promoter for the human FCGR2B is polymorphic, and the less frequent 2B.4 promoter haplotype is associated with the autoimmune phenotype of systemic lupus erythematosus. In the present study, we demonstrate that the 2B.4 promoter haplotype of FCGR2B has increased binding capacity for GATA4 and Yin-Yang1 (YY1) transcription factors in both B lymphocytes and monocytes, and that overexpression of GATA4 or YY1 enhances the FCGR2B promoter activity. The 2B.4 haplotype leads to elevated expression of the endogenous receptor in heterozygous donors by ≈1.5-fold as assessed on EBV-transformed cells, primary B lymphocytes, and CD14+ monocytes. This increased expression accentuates the inhibitory effect of FcγRIIb on B cell Ag receptor signaling, measured by Ca2+ influx and cell viability in B cells. Our results indicate that transcription factors GATA4 and YY1 are involved in the regulation of FcγRIIb expression, and that the expression variants of FcγRIIb lead to altered cell signaling, which may contribute to autoimmune pathogenesis in humans.",
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T1 - A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcγRIIb alters receptor expression and associates with autoimmunity. II. Differential binding of GATA4 and Yin-Yang1 transcription factors and correlated receptor expression and function

AU - Su, Kaihong

AU - Li, Xiaoli

AU - Edberg, Jeffrey C.

AU - Wu, Jianming

AU - Ferguson, Polly

AU - Kimberly, Robert P.

PY - 2004/6/1

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N2 - The immunoreceptor tyrosine-based inhibitory motif-containing FcγRIIb modulates immune function on multiple cell types including B cells, monocytes/macrophages, and dendritic cells. The promoter for the human FCGR2B is polymorphic, and the less frequent 2B.4 promoter haplotype is associated with the autoimmune phenotype of systemic lupus erythematosus. In the present study, we demonstrate that the 2B.4 promoter haplotype of FCGR2B has increased binding capacity for GATA4 and Yin-Yang1 (YY1) transcription factors in both B lymphocytes and monocytes, and that overexpression of GATA4 or YY1 enhances the FCGR2B promoter activity. The 2B.4 haplotype leads to elevated expression of the endogenous receptor in heterozygous donors by ≈1.5-fold as assessed on EBV-transformed cells, primary B lymphocytes, and CD14+ monocytes. This increased expression accentuates the inhibitory effect of FcγRIIb on B cell Ag receptor signaling, measured by Ca2+ influx and cell viability in B cells. Our results indicate that transcription factors GATA4 and YY1 are involved in the regulation of FcγRIIb expression, and that the expression variants of FcγRIIb lead to altered cell signaling, which may contribute to autoimmune pathogenesis in humans.

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