Characterization of the Murine IgG Fc Receptor III and IIB Gene Promoters A SINGLE TWO-NUCLEOTIDE DIFFERENCE DETERMINES THEIR INVERSE RESPONSIVENESS TO C5a

Abstract The two low affinity IgG Fc receptors (FcγR), FcγRIII and FcγRIIB, are coexpressed on myeloid effector cells, and their genes, as reported here, are positively and negatively regulated by both C5a and interferon-γ through different signaling mechanisms. Two 48- and 43-bp sequences (C5a-inductive region (CIR) and C5a-suppressive region (CSR)) in the FcγRIII and FcγRIIB 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-γ-responsive regions in each gene, revealed the presence of a novel element that differs by two nucleotides between FcγRIII and FcγRIIB. Mutation analysis of the CIR and CSR showed that this small difference determines inverse responsiveness in an FcγR 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 FcγRIII and FcγRIIB.