CD70 recruitment to the immunological synapse is dependent on CD20 in B cells

• 成果类型: Article
• 署名作者: Arp, Abbey B.; Gutierrez, Andrea Abel; ter Beest, Martin; Franken, Guus A.; Warner, Harry; Furones, Andrea Rodgers; Kenyon, Angelique N.; Jaeger, Franziska; Cabrera-Orefice, Alfredo; Klaesener, Kathrin; van Deventer, Sjoerd; Droesen, Lenny; Dunlock, Vera Marie E.; Classens, Rene; Staniek, Julian; Borst, Jannie; Reth, Michael; Brandt, Ulrich; Gros, Piet; Kuijpersi, Taco W.; Heemskerk, Mirjam H. M.; Rizzi, Marta; Cano, Laia Querol; van Spriel, Annemiek B.
• 署名单位: Radboud University Nijmegen; Utrecht University; Radboud University Nijmegen; University of Freiburg; University of Freiburg; University of Freiburg; University of Freiburg; Leiden University; Leiden University Medical Center (LUMC); Leiden University; Leiden University Medical Center (LUMC); Emma Children's Hospital; University of Amsterdam; Leiden University; Leiden University Medical Center (LUMC); Medical University of Vienna; University of Freiburg; Johns Hopkins University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10357
• DOI: 10.1073/pnas.2414002122
• 发表日期: 2025-04-22
• 关键词: mhc class-ii; costimulatory ligand cd70; t-cell; dendritic cells; immune synapse; cutting edge; receptor; cd8(+); FAMILY; PATHWAY

摘要

CD20 is a four-transmembrane protein expressed at the surface of B cells from late pro-B cells to memory B cells, with the exception of plasma cells. Its expression pattern makes it an attractive therapeutic target for different B cell malignancies and autoimmune diseases. Despite the clinical success of CD20-targeting antibodies, the biology of the CD20 protein is still not well understood. We investigated CD20 binding partners in the membrane of human B cells using immunoprecipitation followed by mass spectrometry analysis. We identified a molecular interaction between CD70 and CD20, and confirmed this using proximity ligation assays. CD20-CD70 spatiotemporal colocalization was validated at the plasma membrane of B cells using high-resolution microscopy. Cell surface expression of CD70 was found to be enhanced upon CD20 overexpression, suggesting a role for CD20 in stabilizing CD70 at the B cell membrane. Moreover, we observed impaired B-T cell synapse formation and defective recruitment of CD70 to the immunological synapse in the absence of CD20. Impaired synapse formation was confirmed by deleting CD20 in primary B cells, and analysis of B cells from a CD20-deficient patient. Finally, CD20-deletion resulted in diminished T cell activation and cytokine secretion. Together, this study demonstrates that CD20 interacts with CD70 at the B cell membrane, and that CD20 is required for immune synapse formation between B and T cells and consequent T cell activation.