Dennis Bleck, Klara Loacker-Schöch, Tim Classen, Joachim Jose, Matthias Schneider, Georg Pongratz
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引用次数: 0
摘要
类风湿性关节炎(RA)是一种由高度活跃的自身抗体生成 B 细胞驱动的全身性自身免疫疾病。受影响关节中的异位生殖中心可维持 B 细胞的活化。发炎关节中的纤维母细胞样滑膜细胞(FLS)支持 B 细胞的存活、活化和分化。CD27+ 记忆 B 细胞和幼稚 B 细胞对活化,尤其是对 CD40 配体(CD40L)的活化表现出截然不同的反应。我们的研究表明,FLS 依赖性激活人 B 细胞依赖于白细胞介素-6(IL-6)和 CD40L。研究表明,FLS 既能激活幼稚 B 细胞,也能激活记忆 B 细胞。FLS对幼稚B细胞和记忆B细胞的活化潜能是否不同,目前还没有研究。我们的研究结果表明,FLS 诱导的 B 细胞活化依赖于 IL-6 和 CD40L。虽然 FLS 能够诱导记忆 B 细胞的浆细胞分化、同种型转换和抗体生成,但 FLS 激活幼稚 B 细胞的能力却明显较低。
Fibroblast-like synoviocytes preferentially induce terminal differentiation of IgD+ memory B cells instead of naïve B cells
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.
期刊介绍:
Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers.
Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology.
The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.