Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Periodontal Res. 2012 Feb;47(1):105-13. doi: 10.1111/j.1600-0765.2011.01411.x. Epub 2011 Sep 12.
Human FcγRIIb is an immunoglobulin G (IgG) receptor that inhibits the activation of B lymphocytes through cross-linking with the B-cell receptor via immune complexes. This function acts as a negative regulator of antibody production. Our previous studies have demonstrated the gene polymorphisms in FcγRIIb to be associated with periodontitis. In this study, we presented a polymorphism--FcγRIIB-nt645+25A/G (rs2125685)--in intron 4 and analyzed its functional relevance to periodontitis. We examined whether the FcγRIIB-nt645+25A/G polymorphism is associated with periodontal parameters, the IgG response to the periodontopathic bacterium Porphyromonas gingivalis and/or the expression level of FcγRIIb on peripheral B lymphocytes.
Thirty-two patients with chronic periodontitis were genotyped with nested PCR and by direct sequencing of genome DNA. The levels of serum IgG and of specific IgG subclasses for P. gingivalis sonicate and for the recombinant 40-kDa outer membrane protein (OMP) were determined. The expression levels of FcγRIIb on peripheral B lymphocytes from 19 healthy donors were measured by flow cytometry.
Patients with the FcγRIIB-nt645+25AA genotype showed significantly higher mean clinical attachment levels compared to patients with the FcγRIIB-nt645+25GG genotype (p = 0.003) and a significantly lower IgG response to P. gingivalis sonicate and to the 40-kDa OMP. The expression levels of FcγRIIb protein on the cell surface in peripheral B lymphocytes were higher in healthy donors with the FcγRIIB-nt645+25AA genotype than in those with the FcγRIIB-nt645+25GG genotype (p = 0.03).
The higher expression levels of FcγRIIb in subjects with the FcγRIIB-nt645+25AA genotype may induce a lower level of production of IgG against P. gingivalis and therefore more severe periodontitis.
人 FcγRIIb 是一种免疫球蛋白 G(IgG)受体,通过与 B 细胞受体交联形成免疫复合物,从而抑制 B 淋巴细胞的激活。该功能作为抗体产生的负调节剂。我们之前的研究表明,FcγRIIb 的基因多态性与牙周炎有关。在这项研究中,我们提出了一个位于内含子 4 中的多态性——FcγRIIB-nt645+25A/G(rs2125685),并分析了其与牙周炎的功能相关性。我们检测了 FcγRIIB-nt645+25A/G 多态性是否与牙周参数、针对牙周致病菌牙龈卟啉单胞菌的 IgG 反应以及/或外周 B 淋巴细胞上 FcγRIIb 的表达水平有关。
通过巢式 PCR 和基因组 DNA 直接测序对 32 例慢性牙周炎患者进行基因分型。测定血清 IgG 水平和牙龈卟啉单胞菌超声裂解物及重组 40kDa 外膜蛋白(OMP)的特异性 IgG 亚类水平。通过流式细胞术检测 19 名健康供者外周 B 淋巴细胞上 FcγRIIb 的表达水平。
与 FcγRIIB-nt645+25GG 基因型患者相比,FcγRIIB-nt645+25AA 基因型患者的平均临床附着水平显著更高(p = 0.003),对牙龈卟啉单胞菌超声裂解物和 40kDa OMP 的 IgG 反应显著更低。与 FcγRIIB-nt645+25GG 基因型患者相比,FcγRIIB-nt645+25AA 基因型健康供者外周 B 淋巴细胞表面 FcγRIIb 蛋白表达水平更高(p = 0.03)。
FcγRIIB-nt645+25AA 基因型患者 FcγRIIb 的高表达水平可能导致针对牙龈卟啉单胞菌的 IgG 产生水平降低,从而导致更严重的牙周炎。