Characterization of the murine IgG Fc receptor III and IIB gene promoters: a single two-nucleotide difference determines their inverse responsiveness to C5a.

The two low affinity IgG Fc receptors (FcgammaR), FcgammaRIII and FcgammaRIIB, are coexpressed on myeloid effector cells, and their genes, as reported here, are positively and negatively regulated by both C5a and interferon-gamma through different signaling mechanisms. Two 48- and 43-bp sequences (C5a-inductive region (CIR) and C5a-suppressive region (CSR)) in the FcgammaRIII and FcgammaRIIB 5'-flanking regions that are necessary for C5a induction and suppression, respectively, are defined. Sequence analysis of the CIR and CSR, which localize apart from the interferon-gamma-responsive regions in each gene, revealed the presence of a novel element that differs by two nucleotides between FcgammaRIII and FcgammaRIIB. Mutation analysis of the CIR and CSR showed that this small difference determines inverse responsiveness in an FcgammaR gene context-dependent manner. Our study suggests that C5a uses similar DNA motifs (defined as GTGAXXTCCA) in both pathways of transcriptional induction and suppression of FcgammaRIII and FcgammaRIIB.