Centre for Rheumatology and Bloomsbury Rheumatology Unit, Rayne Building, Room 416, University College London, 5 University Street, London WC1E 6JF, UK.
Arthritis Res Ther. 2013;15 Suppl 1(Suppl 1):S3. doi: 10.1186/ar3908. Epub 2013 Mar 25.
In humans, different B-cell subpopulations can be distinguished in peripheral blood and other tissues on the basis of differential expression of various surface markers. These different subsets correspond to different stages of maturation, activation and differentiation. B-cell depletion therapy based on rituximab, an anti-CD20 mAb, is widely used in the treatment of various malignant and autoimmune diseases. Rituximab induces a very significant depletion of B-cell subpopulations in the peripheral blood usually for a period of 6 to 9 months after one cycle of therapy. Cells detected circulating during depletion are mainly CD20 negative plasmablasts. Data on depletion of CD20-expressing B cells in solid tissues are limited but show that depletion is significant but not complete, with bone marrow and spleen being more easily depleted than lymph nodes. Factors influencing depletion are thought to include not only the total drug dose administered and distribution into various tissues, but also B-cell intrinsic and microenvironment factors influencing recruitment of effector mechanisms and antigen and effector modulation. Available studies show that the degree of depletion varies between individuals, even if treated with the same dose, but that it tends to be consistent in the same individual. This suggests that individual factors are important in determining the final extent of depletion.
在人类中，可以根据各种表面标志物的差异表达，在外周血和其他组织中区分不同的 B 细胞亚群。这些不同的亚群对应于不同的成熟、激活和分化阶段。基于抗 CD20 mAb 利妥昔单抗的 B 细胞耗竭疗法广泛用于治疗各种恶性和自身免疫性疾病。利妥昔单抗诱导外周血中 B 细胞亚群的显著耗竭，通常在一个疗程后持续 6 至 9 个月。在耗竭过程中检测到的循环细胞主要是 CD20 阴性浆母细胞。关于实体组织中 CD20 表达 B 细胞耗竭的数据有限，但表明耗竭是显著的，但不是完全的，骨髓和脾脏比淋巴结更容易耗竭。影响耗竭的因素不仅包括给予的总药物剂量和分布到各种组织，还包括影响效应机制募集和抗原及效应物调节的 B 细胞内在和微环境因素。现有研究表明，即使使用相同剂量，个体之间的耗竭程度也存在差异，但在同一个体中趋于一致。这表明个体因素在决定最终耗竭程度方面很重要。
