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Abstract：
BACKGROUND: Ascorbic acid can regulate the function of the immune system. This study aimed to investigate the underlying mechanisms of ascorbic acid in plasma cell differentiation and rheumatoid arthritis (RA).
METHODS: Mice were intraperitoneally injected with either ascorbic acid or an equivalent volume of phosphate-buffered saline (PBS). To elucidate the effects of ascorbic acid on arthritis, we utilized a collagen induced arthritis mouse model (CIA). To investigate the effects of ascorbic acid on antibody response, mice were immunized with (4-Hydroxy-3-nitrophenylacetyl)-Ficoll (NP-Ficoll) or (4-hydroxy-3-nitrophenyl) acetyl-keyhole limpet hemocyanin (NP-KLH) to elicit a T-cell independent (TI) or T-cell dependent (TD) antibody response. To clarify the ability of ascorbic acid on plasma cell production, we tracked the B cell differentiation fate on the NP-specific B1-8hi BCR transgenic background.
RESULTS: Ascorbic acid-injected mice demonstrated significantly delayed disease incidence and decreased disease severity compared to PBS-injected mice. Ascorbic acid can reduce the titers of autoantibodies in both arthritis and lupus mice models. Ascorbic acid can significantly reduce the number of plasma cells and the production of antigen-specific antibodies in TI and TD antibody response. In addition, ascorbic acid can disrupt the antibody affinity maturation. Through B1-8hi adoptive transfer experiments, it has been demonstrated that ascorbic acid restrains B cell differentiation into plasma cells in a cell-intrinsic manner. After in-depth exploration, we found that ascorbic acid can block the cell cycle of B cells and promote cell apoptosis. Mechanistically, ascorbic acid inhibited the production of autoreactive plasma cells by inhibiting the Stat3 signaling pathway.
CONCLUSIONS: Our study demonstrates that ascorbic acid has the ability to suppress the generation of autoreactive plasma cells, diminish the production of autoantibodies, and consequently delay the onset of rheumatoid arthritis.
METHODS: Mice were intraperitoneally injected with either ascorbic acid or an equivalent volume of phosphate-buffered saline (PBS). To elucidate the effects of ascorbic acid on arthritis, we utilized a collagen induced arthritis mouse model (CIA). To investigate the effects of ascorbic acid on antibody response, mice were immunized with (4-Hydroxy-3-nitrophenylacetyl)-Ficoll (NP-Ficoll) or (4-hydroxy-3-nitrophenyl) acetyl-keyhole limpet hemocyanin (NP-KLH) to elicit a T-cell independent (TI) or T-cell dependent (TD) antibody response. To clarify the ability of ascorbic acid on plasma cell production, we tracked the B cell differentiation fate on the NP-specific B1-8hi BCR transgenic background.
RESULTS: Ascorbic acid-injected mice demonstrated significantly delayed disease incidence and decreased disease severity compared to PBS-injected mice. Ascorbic acid can reduce the titers of autoantibodies in both arthritis and lupus mice models. Ascorbic acid can significantly reduce the number of plasma cells and the production of antigen-specific antibodies in TI and TD antibody response. In addition, ascorbic acid can disrupt the antibody affinity maturation. Through B1-8hi adoptive transfer experiments, it has been demonstrated that ascorbic acid restrains B cell differentiation into plasma cells in a cell-intrinsic manner. After in-depth exploration, we found that ascorbic acid can block the cell cycle of B cells and promote cell apoptosis. Mechanistically, ascorbic acid inhibited the production of autoreactive plasma cells by inhibiting the Stat3 signaling pathway.
CONCLUSIONS: Our study demonstrates that ascorbic acid has the ability to suppress the generation of autoreactive plasma cells, diminish the production of autoantibodies, and consequently delay the onset of rheumatoid arthritis.
摘要：
背景：抗坏血酸可以调节免疫系统的功能。本研究旨在探讨抗坏血酸在浆细胞分化和类风湿关节炎(RA)中的作用机制。
方法:小鼠腹膜内注射抗坏血酸或等体积的磷酸盐缓冲盐水(PBS)。为了阐明抗坏血酸对关节炎的影响，我们利用胶原诱导的关节炎小鼠模型(CIA)。为了研究抗坏血酸对抗体反应的影响，用(4-羟基-3-硝基苯基乙酰基)-Ficoll(NP-Ficoll)或(4-羟基-3-硝基苯基)乙酰基-匙孔血蓝蛋白(NP-KLH)免疫小鼠,以引起T细胞非依赖性(TI)或T细胞依赖性(TD)抗体应答。为了阐明抗坏血酸对浆细胞产生的能力，我们在NP特异性B1-8hiBCR转基因背景上跟踪B细胞分化命运。
结果：与注射PBS的小鼠相比，注射抗坏血酸的小鼠表现出明显延迟的疾病发生率和降低的疾病严重程度。抗坏血酸可以降低关节炎和狼疮小鼠模型中自身抗体的滴度。抗坏血酸可显著削减TI和TD抗体反响中浆细胞的数目和抗原特异性抗体的产生。此外,抗坏血酸可以破坏抗体亲和力成熟。通过B1-8hi过继转移实验，已经证明抗坏血酸以细胞固有的方式抑制B细胞分化成浆细胞。经过深入探索,我们发现抗坏血酸可以阻断B细胞的细胞周期，促进细胞凋亡。机械上,抗坏血酸通过抑制Stat3信号通路抑制自身反应性浆细胞的产生。
结论：我们的研究表明，抗坏血酸具有抑制自身反应性浆细胞生成的能力，减少自身抗体的产生，从而延缓类风湿性关节炎的发作。
方法:小鼠腹膜内注射抗坏血酸或等体积的磷酸盐缓冲盐水(PBS)。为了阐明抗坏血酸对关节炎的影响，我们利用胶原诱导的关节炎小鼠模型(CIA)。为了研究抗坏血酸对抗体反应的影响，用(4-羟基-3-硝基苯基乙酰基)-Ficoll(NP-Ficoll)或(4-羟基-3-硝基苯基)乙酰基-匙孔血蓝蛋白(NP-KLH)免疫小鼠,以引起T细胞非依赖性(TI)或T细胞依赖性(TD)抗体应答。为了阐明抗坏血酸对浆细胞产生的能力，我们在NP特异性B1-8hiBCR转基因背景上跟踪B细胞分化命运。
结果：与注射PBS的小鼠相比，注射抗坏血酸的小鼠表现出明显延迟的疾病发生率和降低的疾病严重程度。抗坏血酸可以降低关节炎和狼疮小鼠模型中自身抗体的滴度。抗坏血酸可显著削减TI和TD抗体反响中浆细胞的数目和抗原特异性抗体的产生。此外,抗坏血酸可以破坏抗体亲和力成熟。通过B1-8hi过继转移实验，已经证明抗坏血酸以细胞固有的方式抑制B细胞分化成浆细胞。经过深入探索,我们发现抗坏血酸可以阻断B细胞的细胞周期，促进细胞凋亡。机械上,抗坏血酸通过抑制Stat3信号通路抑制自身反应性浆细胞的产生。
结论：我们的研究表明，抗坏血酸具有抑制自身反应性浆细胞生成的能力，减少自身抗体的产生，从而延缓类风湿性关节炎的发作。
