气候变化领域集成服务门户(CCPortal): CD20 as a gatekeeper of the resting state of human B cells

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DOI	10.1073/pnas.2021342118
	CD20 as a gatekeeper of the resting state of human B cells
	Kläsener K.; Jellusova J.; Andrieux G.; Salzer U.; Böhler C.; Steiner S.N.; Albinus J.B.; Cavallari M.; Süß B.; Voll R.E.; Boerries M.; Wollscheid B.; Reth M.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	CD20 is a B cell-specific membrane protein and represents an attractive target for therapeutic antibodies. Despite widespread usage of anti-CD20 antibodies for B cell depletion therapies, the biological function of their target remains unclear. Here, we demonstrate that CD20 controls the nanoscale organization of receptors on the surface of resting B lymphocytes. CRISPR/Cas9-mediated ablation of CD20 in resting B cells resulted in relocalization and interaction of the IgM-class B cell antigen receptor with the coreceptor CD19. This receptor rearrangement led to a transient activation of B cells, accompanied by the internalization of many B cell surface marker proteins. Reexpression of CD20 restored the expression of the B cell surface proteins and the resting state of Ramos B cells. Similarly, treatment of Ramos or naive human B cells with the anti-CD20 antibody rituximab induced nanoscale receptor rearrangements and transient B cell activation in vitro and in vivo. A departure from the resting B cell state followed by the loss of B cell identity of CD20-deficient Ramos B cells was accompanied by a PAX5 to BLIMP-1 transcriptional switch, metabolic reprogramming toward oxidative phosphorylation, and a shift toward plasma cell development. Thus, anti-CD20 engagement or the loss of CD20 disrupts membrane organization, profoundly altering the fate of human B cells. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	B lymphocyte \| therapeutic antibody \| CD20 \| plasma cell
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180621
作者单位	Biology III, Faculty of Biology, University of Freiburg, Freiburg, 79104, Germany; Centre for Biological Signalling Studies, University of Freiburg, Freiburg, 79110, Germany; Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, 79104, Germany; Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technical University of Munich, Munich, 81675, Germany; lnstitute of Medical Bioinformatics and Systems Medicine, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, 79110, Germany; German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung) Partner Site Freiburg, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, 69120, Germany; Department of Rheumatology and Clinical Immunology, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, 79106, Germany; Department of Health Sciences and Technology, Institute of Translational Medicin...
推荐引用方式 GB/T 7714	Kläsener K.,Jellusova J.,Andrieux G.,et al. CD20 as a gatekeeper of the resting state of human B cells[J],2021,118(7).
APA	Kläsener K..,Jellusova J..,Andrieux G..,Salzer U..,Böhler C..,...&Reth M..(2021).CD20 as a gatekeeper of the resting state of human B cells.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Kläsener K.,et al."CD20 as a gatekeeper of the resting state of human B cells".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).