Ligand binding specificities and signal transduction pathways of Fcγ receptor IIc isoforms:: the CD32 isoforms expressed by human NK cells

We recently reported that human NK cells express, in addition to CD16 [Fc gamma receptor (Fc gamma R) IIIA], a second type of Fc gamma R, namely CD32 (Fc gamma RII). Molecular characterization of CD32 transcripts expressed by highly purified NK cells revealed that they predominantly express products of the Fc gamma RIIC gene. Using stable Jurkat transfectants we have analyzed the functional properties of two Fc gamma RIIc-specific isoforms isolated from NK cells, namely Fc gamma RIIc1 and Fc gamma RIIc3, which differ in their cytoplasmic tails. The ligand binding specificity for both murine and human IgG isotypes was found to be similar to that observed for Fc gamma RIIb isoforms. Immunoprecipitation studies of Fc gamma RIIc isoforms expressed in Jurkat cells revealed a protein of around 40 kDa for Fc gamma RIIc1, and a protein of around 32 kDa for Fc gamma RIIc3. Signal transduction studies performed on Fc gamma RIIc1-expressing Jurkat cells indicated that this molecule is functional, i.e. capable of Ca2+ mobilization and activation of Lck, Zap-70 and Syk protein tyrosine kinases, although the CD3 zeta chain was not found to functionally associate with Fc gamma RIIc1. In contrast, Fc gamma RIIc3 transfectants showed an impaired ability of this molecule to mobilize Ca2+, but activation of Lck was detected following activation via Fc gamma RIIc3. These studies demonstrate the functional activity of Fc gamma RIIc isoforms and suggest that the presence of CD32, in addition to CD16, on NK cells may have functional relevance.