Fcgr2b基因及H-2复合体对SLE模型小鼠IgG抗体产生的调节作用

Effects of Fcgr2b and H-2 complex on production of serum IgG antibodies in systemic lupus erythematosus model

目的:分析Fcgr2b基因对SLE小鼠血清总IgG抗体产生的影响;Fcgr2b基因单独及Fcgr2b基因与H-2复合体共同作用对SLE小鼠血清IgG抗DNA抗体产生的调控。方法:建立(NZB×NZW)F1×NZW回交小鼠模型,用特异性荧光抗体染色,流式细胞术检测及PCR技术进行基因分型,以ELISA法测定血清总IgG及抗DNA抗体水平进行分析比较。采用扩增片段长度多态性(AmpFLP)分析NZB,NZW小鼠Fcgr2b基因启动子区是否有多态性。结果:(NZB×NZW)F1×NZW回交小鼠Fc-gr2b基因B/W型组血清总IgG水平明显高于W/W型组(P<0.0001)。Fcgr2b基因独作用时,回交小鼠Fcgr2b基因B/W型组与W/W型组间血清IgG抗DNA抗体水平差异不显著(P>0.05)。Fcgr2b基因与H-2复合体共同作用时,H-2复合体为d/z型时,无论Fcgr2b基因是B/W型或W/W型,其血清IgG抗DNA抗体水平明显高于含H-2复合体Z/Z型组(P<0.01);H-2复合体为d/z型时,含Fcgr2b基因B/W型组血清IgG抗DNA抗体水平明显高于W/W型组(P<0.01)。NZB小鼠Fcgr2b基因启动子区扩增片段长度短于非自身免疫病小鼠NZW,C57BL/6及BALB/c小鼠,提示可能存在碱基缺失。结论:血清总IgG水平由Fcgr2b基因调控;IgG抗DNA抗体产生主要由H-2复合体调控,Fcgr2b基因单独作用对该抗体产生的影响不明显,但与H-2复合体具有协同作用。

Objective： To analyze the effect of Fcgr2b gene on production of serum total IgG antibody. To compare the effects of Fcgr2b allele and H-2 complex on production of serum IgG antibodies in systemic lupus erythematosus（SLE）models-（NZB×NZW）F1 mice.Methods： The model of （NZB×NZW）F1×NZW backcross mice was set up and gene typing was made with specific fluorescence staining,flow eytometry and PCR.Serum total IgG and IgG anti-DNA antibodies were measured by ELISA.Amplified fragment length polymorphism（AmpFLP） analysis was used to observe the polymorphism of Fcgr2b promoter region among NZB, NZW mice. Results-Serum total IgG of the group of Fegr2b gene B/W type was obviously higher than that of W/W type（ P 〈 0.0001）. The level of serum IgG anfi-DNA antibodies had no significant difference between the group of Fegr2b B/W type and W/W type（ P〉0.05） .The level of serum IgG anti-DNA antibodies was signefieantly higher in the group of H-2 complex d/z type, Fcgr2b B/W and d/z,W/W type than that of H-2 complex z/z, Fcgr2b B/W and z/z,W/W type.The level of IgG anti-DNA antibodies was significantly higher in the group of Fcgr2b B/W, H-2 complex d/z type than that of W/W, d/z type. AmpFLP of Fegr2b promoter region in NZB mice was shorter than that of non-autoimmune NZW and BALB/c mice and indicates the deletion in Fegr2b prorooter region in NZB mice. Conclusions：The level of serum IgG antibodies might be mainly controlled by Fcgr2b. The production of serum IgG anfi-DNA antibodies might be mainly eomtrolled by H-2 complex. Frgr2b alone could mot affect the producing of IgG anti-DNA antibodies, but Fegr2b and H-2 complex could present the synergism effect on producing of IgG anfi-DNA antibodies.