Variant FCGR3 genes: transcription and possible origins.

ABSTRACT

The Fc receptors for human immunoglobulin G (FcgammaR) IIIb are encoded by genes clustered on the long arm of chromosome 1 (band q21 --> 24) and exhibit allelic polymorphisms. Several rare FCGR3B sequences were identified in both white and black donors. However, the origins of these genomic variants are unknown and their transcription has not yet been investigated. Blood from a donor with known FCGR3 variants was used to extract DNA from peripheral blood CD34+ cells, CD19+ B-cells, neutrophils and buccal cells, after which FCGR3 gene sequencing was performed. Additionally, RNA samples from 5 Caucasian individuals containing known variant FCGR3 genes were reverse-transcribed to cDNA and the FCGR3 genes were sequenced. Our results showed that the frequencies of variant clones were higher in B-cell preparations than in CD34+ hematopoietic progenitor cells from peripheral blood and neutrophils. Very high variant frequencies were found in buccal cell-derived clones. Variant cDNA sequences were identified in three of five individuals with known FCGR3 variants. We conclude that FCGR3 gene variants are differentially transcribed between cell types and tissues, increasing the likelihood of the presence of variant FcgammaRIII receptors on the cell surface. The significance of the high number of variant clones in buccal cells, however, is unclear.