THE HUMAN LOW-AFFINITY IMMUNOGLOBULIN-G FC RECEPTOR III-A AND III-B GENES - MOLECULAR CHARACTERIZATION OF THE PROMOTER REGIONS

The human Fc receptor with low affinity for IgG (Fc gamma RIII, CD16) is encoded by two nearly identical genes, Fc gamma RIII-A and Fc gamma RIII-B, resulting in tissue-specific expression of alternative membra ne-anchored isoforms, The transmembrane CD16 receptor forms a heterome ric structure with the Fc epsilon RI (gamma) and/or CD3 (zeta) subunit s on the surface of activated monocytes/macrophages, NK cells, and a s ubset of T cells, The expression of the glycosylphosphatidylinositol-a nchored CD16 isoform encoded by the Fc gamma RIII-B gene is restricted to polymorphonuclear leukocytes and can be induced by Me(2)SO differe ntiation of HL60 cells, We have isolated and sequenced genomic clones of the human Fc gamma RIII-A and Fc gamma RIII-B genes, located their transcription initiation sites, identified a different organization of their 5' regions, and demonstrated four distinct classes of Fc gamma RIII-A transcripts (a1-a4) com pared with a single class of Fc gamma R III-Bb1 transcripts, Both CD16 promoters (positions -198 to -10) lack the classical ''TATA'' positioning consensus sequence but confer trans criptional activity when coupled to the human lysozyme enhancer, Both promoters also display different tissue-specific transcriptional activ ities reflecting the expected gene expression of Fc gamma RIII-A and F c gamma RIII-B in NH cells versus polymorphonuclear leukocytes. Within the -198/-10 fragments, the sequences of the two CD16 genes have been identified to differ in 10 positions. It is suggested that these nucl eotide differences might contribute to cell type-specific transcriptio n of Fc gamma RIII genes.