The alternatively spliced CD64 transcript Fc gamma Rlb2 does not specify asurface-expressed isoform

Three highly homologous genes (A, B and C) and six transcripts have been id entified for the class I human IgG receptor (CD64). The hFc gamma Rla1 isof orm encodes the prototypic high-affinity receptor for IgG. The alternativel y spliced hFc gamma Rlb2 transcript was postulated to exist as a second sur face-expressed CD64 isoform on myeloid cells. In this report we assessed th is proposed role for hFc gamma Rlb2 in detail. As CD64 monoclonal antibodie s might not recognize hFc gamma Rlb2, we tagged the receptor with an hemagg lutinin tag and transfected hFc gamma Rlb2tag in the presence of FcR gamma- chain into IIA1.6 cells. Both transcript and protein of hFc gamma Rlb2tag w ere clearly present in transfectants. However, in contrast to the (control) hFc gamma Rla1tag, no surface expression of hFc gamma Rlb2tag was detectab le with a tag-specific monoclonal antibody. Confocal scan laser microscopy revealed hFc gamma Rlb2tag to be retained in the endoplasmic reticulum, res ulting in absent plasma membrane expression. These results show hFc gamma R lb2 neither to be surface expressed, nor to represent a separate CD64 isofo rm. This finding, furthermore, implicates that other FcR transcripts define d at the mRNA level may not represent true FcR isoforms either.