Department of Immunology, Hannover Medical School, Federal Republic of Germany.
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 membrane-anchored isoforms. The transmembrane CD16 receptor forms a heteromeric structure with the Fc epsilon RI (gamma) and/or CD3 (zeta) subunits on the surface of activated monocytes/macrophages, NK cells, and a subset of T cells. The expression of the glycosylphosphatidylinositol-anchored CD16 isoform encoded by the Fc gamma RIII-B gene is restricted to polymorphonuclear leukocytes and can be induced by Me2SO differentiation 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) compared with a single class of Fc gamma RIII-Bb1 transcripts. Both CD16 promoters (positions -198 to -10) lack the classical "TATA" positioning consensus sequence but confer transcriptional activity when coupled to the human lysozyme enhancer. Both promoters also display different tissue-specific transcriptional activities reflecting the expected gene expression of Fc gamma RIII-A and Fc gamma RIII-B in NK 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 nucleotide differences might contribute to cell type-specific transcription of Fc gamma RIII genes.