Proper regulation of B-cell function is essential for effective humoral immunity and maintenance of immune tolerance. Here, we found that FBW7 (F-box/WD40 repeat-containing protein 7) is highly expressed in germinal centre B and B1 cells, and confirmed that it has an intrinsic role in maintaining homeostasis of mature B cells and B-1 cells. FBW7 deletion led to an impairment of antibody response, and although germinal centre formation was not affected, antibody class-switch recombination and affinity maturation processes were defective. Likewise, memory immune response was severely impaired. Moreover, FBW7 ablation ameliorated the pathogenesis of an autoimmune disease model, collagen-induced arthritis, by reducing the production of anti-collagen II autoantibodies. Taken together, these data suggest that FBW7 may be an attractive target for developing new therapeutics for the treatment of autoimmune diseases.

中文翻译：

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E3泛素连接酶FBW7在B细胞反应和实验性自身免疫性关节炎发病机制中的关键作用

适当调节 B 细胞功能对于有效的体液免疫和维持免疫耐受至关重要。在这里，我们发现 FBW7（F-box/WD40 重复蛋白 7）在生发中心 B 和 B1 细胞中高表达，并证实它在维持成熟 B 细胞和 B-1 细胞的稳态中具有内在作用。FBW7 缺失导致抗体反应受损，尽管生发中心形成不受影响，但抗体类别转换重组和亲和力成熟过程存在缺陷。同样，记忆免疫反应严重受损。此外，FBW7 消融通过减少抗胶原蛋白 II 自身抗体的产生，改善了自身免疫性疾病模型胶原诱导性关节炎的发病机制。综合起来，