CD20 is a B cell specific membrane protein and a target of therapeutic antibodies such as rituximab (RTX). In spite of the prominent usage of anti-CD20 antibodies in the clinic little is known about the biological function of CD202. Here we show that CD20 controls the nanoscale organization of receptors on the surface of resting B lymphocytes. A CRISPR/Cas-based ablation of CD20 in Ramos B cells results in a relocalisation of the IgM B cell antigen receptor (IgM-BCR) and the co-receptor CD19. The resulting IgM-BCR/CD19 signaling synapse leads to transient B cell activation followed by plasma cell differentiation. Similarly to CD20-deficient Ramos cells, naive human B cells treated with rituximab in vitro or isolated from patients during rituximab administration display hallmarks of transient activation characterized by the formation of the IgM-BCR/CD19 signaling synapse, followed by CD19 and IgM-BCR downregulation. Moreover, increased expression of specific plasma cell genes can be observed after rituximab treatment in relapsed CLL patients. In summary we identify CD20 as a gatekeeper of the resting state on human B cells and demonstrate that a disruption of the nanoscale organization of the B cell surface via CD20 deletion or anti-CD20 treatment profoundly alters B cell fate.

中文翻译：

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CD20作为人类B细胞静止期的守门人

CD20是B细胞特异性膜蛋白，是治疗性抗体（如rituximab（RTX））的靶标。尽管抗CD20抗体在临床上得到了广泛应用，但对CD202的生物学功能知之甚少。在这里，我们显示CD20控制静止B淋巴细胞表面上受体的纳米级组织。Ramos B细胞中基于CRISPR / Cas的CD20消融导致IgM B细胞抗原受体（IgM-BCR）和共受体CD19重新定位。产生的IgM-BCR / CD19信号突触导致短暂的B细胞活化，随后是浆细胞分化。与缺乏CD20的Ramos细胞相似，体外用利妥昔单抗治疗或在利妥昔单抗给药期间从患者体内分离的天然人类B细胞表现出短暂激活的特征，其特征在于形成IgM-BCR / CD19信号突触，随后CD19和IgM-BCR下调。此外，在利妥昔单抗治疗后的复发性CLL患者中，可以观察到特定浆细胞基因的表达增加。总而言之，我们将CD20鉴定为人类B细胞上静止状态的守门人，并证明通过CD20缺失或抗CD20处理破坏B细胞表面的纳米级组织将极大地改变B细胞的命运。