Firth Matthew A, Chattha Kuldeep S, Hodgins Douglas C, Shewen Patricia E
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Vet Immunol Immunopathol. 2010 May 15;135(1-2):43-51. doi: 10.1016/j.vetimm.2009.10.029. Epub 2009 Dec 14.
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.
免疫球蛋白分子Fc段受体（FcR）在循环抗体与细胞效应功能之间提供了重要且关键的联系。这些受体在人类和鼠类中已得到充分表征，但在牲畜中对这些受体的研究较少。FcγRII（CD32）是一种FcR，先前在小鼠和人类中显示存在多种同种型，包括激活型（FcγRIIa、FcγRIIc）和抑制型（FcγRIIb），存在于多种细胞上，包括B细胞、T细胞、树突状细胞、单核细胞、巨噬细胞和血小板。在B细胞上，FcγRIIb通过基于免疫受体酪氨酸的抑制基序信号结构域抑制细胞活化和免疫球蛋白产生。FcγRIIb的两种亚型，命名为b1和b2，在人类和小鼠中已得到证实，b1型包含一个额外的细胞质外显子，而在牛中仅鉴定出一种与人类和小鼠b2亚型相对应的序列。在本研究中，通过采集奶牛和肉牛品种成年牛的血样，并通过RT-PCR测定其FcγRIIb mRNA表达谱，对牛血单核细胞中FcγRIIb的表达谱进行了表征。分析显示，除了先前发表的单一转录本外，还存在两种未表征的牛FcγRIIb转录本。对第一个未知转录本的分析显示与已发表的人类和鼠类FcγRIIb1序列具有高度同源性。该转录本存在于所有检测的细胞类型中，个体之间或品种之间的一级序列差异很小。发现第二个未知序列与鼠类FcγRIIb3（人类中的IgG结合蛋白或可溶性FcγR）序列同源。该转录本的表达谱似乎更为有限，这可能表明表达随细胞的细胞活化状态而变化。这些结果表明，牛与人类和小鼠一样，表达多种FcγRIIb亚型。这些发现进一步增加了IgG介导免疫调节的复杂性，并为Fc受体在牛抗原获取和呈递中的作用提供了新的见解。
