Porcine FcγRIII isoforms are generated by alternative splicing

The FcγRIII plays an essential role in antibody-mediating effector functions of immune cells. Here, we report that transcripts encoding porcine FcγRIII isoforms are generated by alternative splicing. FcγRIII a.1 is expressed on the cell surface while FcγRIII a.2 is secreted from the transfected cells due to a partial deletion of the transmembrane domain. Interestingly, a putative soluble FcγRIII (sCD16) is detected in circulating plasma. Both FcγRIII a.2 and sCD16 exhibit a similar molecular mass (∼35 kDa) and contain the extracellular D2 domains that are structurally intact. Despite the D2 domain deletion, FcγRIII a.3 associates with FcγRIII a.1. Hence, these results suggest one possibility that three FcγRIII isoforms differentially modulate FcγRIII-mediated immune responses in the porcine system. Furthermore, we demonstrate that a cytolytic triggering G7 monoclonal antibody recognizes the D2 domain that is responsible for interacting with the immune complexes and subsequent activations of porcine innate immune cells. This result suggests that the D2 domain is a target region to develop therapeutic antibodies that regulate the FcR-mediated immune responses.