期刊
JOURNAL OF IMMUNOLOGY
卷 172, 期 11, 页码 7192-7199出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.172.11.7192
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资金
- NCRR NIH HHS [M01 RR00032] Funding Source: Medline
- NIAMS NIH HHS [R01 AR42476, P01 AR49084, P30 AR48311, P50 AR45231] Funding Source: Medline
- PHS HHS [R01 33062] Funding Source: Medline
The immunoreceptor tyrosine-based inhibitory motif-containing FcgammaRIIb 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 approximate to1.5-fold as assessed on EBV-transformed cells, primary B lymphocytes, and CD14(+) monocytes. This increased expression accentuates the inhibitory effect of FcgammaRIIb 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 FcgammaRIIb expression, and that the expression variants of FcgammaRIIb lead to altered cell signaling, which may contribute to autoimmune pathogenesis in humans.
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