B cells play a crucial role as antigen-presenting cells and collaborate with inflammatory cytokines in glucose-6-phosphate isomerase-induced arthritis
B cells play a crucial role as antigen-presenting cells and collaborate with inflammatory cytokines in glucose-6-phosphate isomerase-induced arthritis
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DOI：
10.1111/j.1365-2249.2008.03816.x
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发表时间：
2009-02-01
影响因子：
4.6
通讯作者：
Sumida, T.
中科院分区：
文献类型：
--
作者：
Tanaka-Watanabe, Y.;Matsumoto, I.;Sumida, T.
来自K/BxN小鼠的抗葡萄糖-6-磷酸异构酶（GPI）抗体直接诱导关节炎;然而，来自GPI诱导的关节炎小鼠的这些抗体的转移不会诱导关节炎。在该模型中，CD 4（+）T细胞在诱导期和效应期发挥重要作用;然而，B细胞和免疫球蛋白（Ig）的作用尚未阐明。本研究采用过继性移植的方法，观察了B细胞和Ig在GPI诱导的SCID小鼠关节炎中的作用。将用GPI免疫的雄性DBA/1小鼠的脾细胞转移到SCID小鼠中，在后者中在第6天诱导关节炎，与抗GPI抗体的产生相关联。在关节炎SCID小鼠中鉴定了C3和IgG在关节表面上的共定位。从患关节炎的DBA/1小鼠中接种IgG（或抗GPI抗体）和CD 19（+）耗尽的脾细胞在SCID小鼠中诱导关节炎，但从DBA/1小鼠中接种CD 19（+）耗尽或CD 4（+）耗尽的脾细胞不诱导关节炎。对DBA/1关节炎小鼠脾细胞细胞因子产生的体外分析表明，以抗原特异性方式产生大量肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6（P < 0.01），且CD 19（+）耗竭的脾细胞比CD 4（+）耗竭的脾细胞占主导地位（P < 0.05）。向培养物中添加来自DBA/1关节炎小鼠的IgG可增强TNF-α而非IL-6的产生，并且这种作用可被抗Fc γ受体抗体阻断。在SCID小鼠中用TNF-α中和完全保护关节炎的体内分析。我们的结果强调了B细胞作为自身抗体产生者在GPI诱导的关节炎中的重要作用，并且这些自身抗体可以与炎性细胞因子（尤其是TNF-α）协同触发关节炎症。
Anti-glucose-6-phosphate isomerase (GPI) antibodies from K/BxN mice directly induce arthritis; however, the transfer of these antibodies from mice with GPI-induced arthritis does not induce arthritis. CD4(+) T cells play an important role in the induction and effector phase in this model; however, the roles of B cells and immunoglobulins (Igs) have not been elucidated. We investigated the roles of B cells and Igs in GPI-induced arthritis by using adoptive transfer system into SCID mice. Transfer of splenocytes of male DBA/1 mice immunized with GPI into SCID mice induced arthritis on day 6 in the latter, in association with the production of anti-GPI antibodies. Co-localization of C3 and IgG on the articular surface was identified in arthritic SCID mice. Inoculation of IgG (or anti-GPI antibodies) and CD19(+)-depleted splenocytes from arthritic DBA/1 mice induced arthritis in SCID mice, but not CD19(+)-depleted or CD4(+)-depleted splenocytes from DBA/1 mice. In vitro analysis of cytokine production by splenocytes from DBA/1 arthritic mice demonstrated production of large amounts of tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 in an antigen-specific manner (P < 0.01), and production was dominated by CD19(+)-depleted than CD4(+)-depleted splenocytes (P < 0.05). Addition of IgG from DBA/1 arthritic mice to the culture enhanced TNF-alpha but not IL-6 production, and this effect was blocked by anti-Fc gamma receptor antibody. In vivo analysis of neutralization with TNF-alpha protected arthritis completely in SCID mice. Our results highlight the important role of B cells in GPI-induced arthritis as autoantibody producers, and these autoantibodies can trigger joint inflammation in orchestration with inflammatory cytokines, especially TNF-alpha.