Clinic for Rheumatology, Medical Faculty of Heinrich Heine University, University Hospital Düsseldorf, Düsseldorf, Germany.
Hiller Research Center, Medical Faculty of Heinrich Heine University, University Hospital Düsseldorf, Düsseldorf, Germany.
Immunology. 2024 Nov;173(3):520-535. doi: 10.1111/imm.13840. Epub 2024 Jul 25.
Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by highly active autoantibody-producing B cells. Activation of B cells is maintained within ectopic germinal centres found in affected joints. Fibroblast-like synoviocytes (FLS) present in inflamed joints support B-cell survival, activation, and differentiation. CD27+ memory B cells and naive B cells show very different responses to activation, particularly by CD40 ligand (CD40L). We show that FLS-dependent activation of human B cells is dependent on interleukin-6 (IL-6) and CD40L. FLS have been shown to activate both naive and memory B cells. Whether the activating potential of FLS is different for naive and memory B cells has not been investigated. Our results suggest that FLS-induced activation of B cells is dependent on IL-6 and CD40L. While FLS are able to induce plasma cell differentiation, isotype switching, and antibody production in memory B cells, the ability of FLS to activate naive B cells is significantly lower.
类风湿关节炎（RA）是一种由高度活跃的产生自身抗体的 B 细胞驱动的系统性自身免疫性疾病。B 细胞的激活在受影响的关节中发现的异位生发中心内得到维持。存在于炎症关节中的成纤维样滑膜细胞（FLS）支持 B 细胞的存活、激活和分化。CD27+记忆 B 细胞和幼稚 B 细胞对激活的反应非常不同，特别是对 CD40 配体（CD40L）的反应。我们表明，FLS 依赖性的人 B 细胞激活依赖于白细胞介素 6（IL-6）和 CD40L。已经表明 FLS 可以激活幼稚 B 细胞和记忆 B 细胞。FLS 对幼稚 B 细胞和记忆 B 细胞的激活潜力是否不同尚未得到研究。我们的结果表明，FLS 诱导的 B 细胞激活依赖于 IL-6 和 CD40L。虽然 FLS 能够诱导记忆 B 细胞中的浆细胞分化、同种型转换和抗体产生，但 FLS 激活幼稚 B 细胞的能力要低得多。
