title: Multiple bovine FcgammaRIIb sub-isoforms generated by alternative splicing.
abstract: Receptors for the Fc portion of immunoglobulin molecules (FcR) provide an important and vital link between circulating antibody and cellular effector functions. These receptors have been well characterized in human and murine species, however few of these receptors have been investigated in livestock. FcgammaRII (CD32) is an FcR previously shown in mice and humans to exist in multiple isoforms, both activating (FcgammaRIIa, FcgammaRIIc) and inhibitory (FcgammaRIIb), on a wide variety of cells including B cells, T cells, dendritic cells, monocytes, macrophages and platelets. On B cells, FcgammaRIIb acts to suppress cell activation and immunoglobulin production by means of an intracellular immunoreceptor tyrosine-based inhibitory motif signaling domain. Two sub-isoforms of FcgammaRIIb, designated b1 and b2, distinguished by the inclusion of an additional cytoplasmic exon in the b1 form, have been demonstrated in humans and mice, whereas only one sequence corresponding to the human and mouse b2 isoform has been identified in cattle. In this study, the expression profile of FcgammaRIIb in bovine blood mononuclear cells was characterized by collecting blood samples from mature cattle of dairy and beef breeds, and determining their FcgammaRIIb mRNA expression profile by RT-PCR. Analysis revealed the presence of two uncharacterized bovine FcgammaRIIb transcripts in addition to the single previously published transcript. Analysis of the first unknown transcript revealed high homology with published human and murine FcgammaRIIb1 sequences. This transcript was present in all cell types examined, with little variation in primary sequence between individuals or among breeds. The second unknown sequence was found to be homologous to the murine FcgammaRIIb3 (IgG-binding protein or soluble FcgammaR in humans) sequence. This transcript appears to have a much more limited expression profile, which may indicate that expression varies with the cellular activation-state of the cell. These results indicate that cattle, like humans and mice, express multiple sub-isoforms of FcgammaRIIb. These findings add further complexity to the regulation of IgG-mediated immunity and provide new insight into the role Fc receptors play in antigen acquisition and presentation in cattle.
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Electronic address: mfirth@uoguelph.ca.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Firth
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Kuldeep S
authors.initials: KS
authors.lastname: Chattha
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Hodgins
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Shewen
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000276:immunology; D000818:Animals; D002417:Cattle / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry / Q000662:veterinary; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: C080571:Fc gamma receptor IIB; D020033:Protein Isoforms; D017452:Receptors, IgG