Porcine Fc gamma RIIb sub-isoforms are generated by alternative splicing

Abstract

Receptors for the Fc portion of IgG (FcγRs) are expressed on various leukocytes and they modulate both humoral and cell-mediated immune responses with different capacities for IgG binding and phagocytosis. Four different types of FcγRs, FcγRI (CD64), FcγRII (CD32), FcγRIII (CD16) and FcγRIV, have been identified. There are three FcγRII isoforms (activating FcγRIIa and FcγRIIc, and inhibitory FcγRIIb) in humans, one isoform (inhibitory FcγRIIb) in mice, and two isoforms (inhibitory FcγRIIb and activating FcγRIIc) in cattle. Two alternativly spliced isoforms of FcγRIIb, b1 and b2, have been identified in humans, mice and cattle, however, only two porcine FcγRIIb transcripts have been reported. In this study, we report the identification of three new porcine FcγRIIb transcript and analyze the sequences of five porcine FcγRIIb transcript generated by alternative splicing. The porcine transcript 1 and porcine transcript 2 have a high homology and structural similarity with human b1 and b2, respectively, while there is only one alanine residue difference at the signal peptide region between porcine transcript 1 and transcript 4, as well as porcine transcript 2 and transcript 3. This is the first time that an alternativly spliced isoform of porcine transcript 5 is described in pigs rather than humans or other animals. All the five transcripts have the consensus sequence of an ITIM (ITYSLL) in their cytoplasmic tails. Analysis results indicate that the five transcripts serve as inhibitory receptors and are these sub-isoforms or alternativly spliced isoforms. Immunoglobulin-binding assays show that transcript 1, transcript 2, transcript 3 and transcript 4 have binding activity for IgG immune complexes, whereas transcripts 5 without domain 2 can not bind IgG-complexes. It is now clear that porcine FcγRIIb exists as five sub-isoforms at least. These sub-isoforms may individually modulate FcγRIIb-mediated immune responses in the porcine immune system.