探讨高脂饮食（high fat diet， HFD）诱导肥胖对胶原诱导性关节炎（collagen-induced arthritis， CIA）小鼠体液免疫应答的影响及机制。通过给予C57BL/6小鼠喂饲高脂肪成分饲料（40%）构建小鼠肥胖模型，在此基础上构建小鼠CIA模型。通过临床积分、病理组织染色评估CIA小鼠疾病活动度；应用microCT分析骨质骨量情况；ELISA检测血清炎性因子和免疫球蛋白水平；流式细胞术分析T、B淋巴细胞亚群。进一步采用腹腔注射T细胞依赖性抗原4-羟基-3-硝基苯基乙酰基（NP）嵌合的钥孔嘁血蓝素（NP-KLH）及非T细胞依赖性抗原NP-Ficoll来评估HFD小鼠对抗原的免疫应答能力。结果显示，短期HFD促进CIA小鼠体质量增加，血清中瘦素和IL-6升高，并显著降低CIA小鼠关节炎的发病率，减轻关节滑膜区炎性细胞浸润程度和关节、胫骨的骨质破坏。HFD显著下调CIA小鼠的血清免疫球蛋白（IgG1、IgG2b和IgG3）和B细胞亚群（B220⁺IgM⁺IgD^-和B220⁺CD5⁺CD11b⁺B细胞）的产生。此外，HFD显著减弱了小鼠对免疫原的应答，特别是对T细胞依赖性抗原及免疫球蛋白的产生能力。因此短期HFD可通过降低B细胞的数量、减弱机体对抗原的免疫应答能力而降低CIA的发生和发展。由此饮食可能是调控慢性炎症状态和体液免疫应答的重要影响因素。

To investigate the effect of high fat diet (HFD)-induced obesity on the humoral immune response in mice with collagen-induced arthritis (CIA), male C57BL/6 mice fed with HFD (40% fat) or normal diet (10% fat) for six weeks were subcutaneously injected with chicken type Ⅱ collagen to establish the CIA mice model. Clinical scoring of hind paw swelling was assessed as the disease severity in CIA mice. Pathological changes in the hind paws of CIA mice were assessed by histological examination on sections stained with haematoxylin and eosin (HE), tartrate-resistant acid phosphatase (TRAP), and Safranin O. Bone mineral densities and bone morphometric parameters were evaluated by micro-CT. Serum levels of inflammatory cytokines and immunoglobulins were determined by ELISA. Splenic T and B cells were analyzed using flow cytometry. Furthermore, we evaluated the ability of these HFD or normal diet-fed mice to develop immune responses to T cell-dependent antigen (4-Hydroxy-3-nitrophenylacetyl-Keyhole Lymphocyte Hemocyanin, NP-KLH) and T cell-independent antigen (NP-Ficoll). HFD increased the body weight of CIA mice and serum levels of leptin and IL-6. However, HFD inhibited the incidence of arthritis and bone destruction of CIA mice by reducing the infiltration of inflammatory immune cells into joints. Both pathogenic collagen type Ⅱ-specific mouse antibodies (IgG1/IgG2b/IgG3) and B220⁺IgM⁺IgD^- / B220⁺CD5⁺CD11b⁺B cells were down-regulated in mice fed with HFD. Importantly, the humoral immune responses against antigens, especially T cell-dependent antigens, were significantly reduced in HFD-fed mice compared to those of normal diet fed mice. In brief, short-term administration of HFD could prevent the occurrence and disease severity of CIA in mice by suppressing the development of pathogenic B lymphocyte subsets and the humoral immune response. Our findings uncover a novel mechanism by which dietary factors regulating the humoral immune response．