Department of Internal Medicine II-Nephrology, University Hospital Regensburg, Regensburg, Germany.
Division of Genetics, Department of Biology, University Erlangen-Nuernberg, Erlangen, Germany.
Eur J Immunol. 2022 Apr;52(4):656-668. doi: 10.1002/eji.202149523. Epub 2022 Jan 11.
B cells play a major role in the pathogenesis of many autoimmune diseases like MS, rheumatoid arthritis, or systemic lupus erythematosus. Depletion of B cells with anti-CD20 antibodies is an established therapy for MS. However, total B-cell depletion will also affect regulatory B cells that are known to suppress autoimmune responses. In our studies, we describe an alternative approach based on targeting CD79b that induces only partial B-cell depletion and achieves therapeutic effects by B-cell modulation. Prophylactic and therapeutic treatment with an antibody against CD79b and also a deglycosylated variant of this antibody, lacking effector function like antibody-dependent cellular cytotoxicity or complement activation, significantly reduced the development and progression of EAE in mice. Our data show that modulation of B cells via CD79b is equally effective as almost complete B-cell depletion with anti-CD20 antibodies and may constitute an alternative approach to treat MS.
B 细胞在多发性硬化症、类风湿关节炎或系统性红斑狼疮等许多自身免疫性疾病的发病机制中起主要作用。用抗 CD20 抗体耗竭 B 细胞是多发性硬化症的一种既定治疗方法。然而,总 B 细胞耗竭也会影响已知抑制自身免疫反应的调节性 B 细胞。在我们的研究中,我们描述了一种基于针对 CD79b 的替代方法,该方法仅诱导部分 B 细胞耗竭,并通过 B 细胞调节来实现治疗效果。用针对 CD79b 的抗体以及该抗体的去糖基化变体(缺乏抗体依赖的细胞毒性或补体激活等效应功能)进行预防和治疗性治疗,可显著减少小鼠 EAE 的发生和进展。我们的数据表明,通过 CD79b 调节 B 细胞与用抗 CD20 抗体几乎完全耗竭 B 细胞同样有效,可能是治疗多发性硬化症的一种替代方法。