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

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.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-04-15
DOI
https://doi.org/10.1073/pnas.2414002122
Citations
3
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
2.39

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article

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

René Classens, Taco W. Kuijpers, Michael Reth, Kathrin Kläsener et al.
3 citations
Proceedings of the National Academy of Sciences
T-cell and B-cell Immunology
2.39
article

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

René Classens, Taco W. Kuijpers, Michael Reth, Kathrin Kläsener, Marta Rizzi, Julian Staniek, Andrea Rodgers Furones, Martin ter Beest, Annemiek B. van Spriel, Ulrich Brandt, Piet Gros, Laia Querol Cano, Alfredo Cabrera‐Orefice, Jannie Borst, Angelique N. Kenyon, Sjoerd van Deventer, Harry Warner, Franziska Jäger, Vera-Marie E. Dunlock, Aura V. Gutiérrez, Abbey B. Arp, Lenny Droesen, Mirjam H.M. Heemskerk, Guus A. Franken
article en
3 citations

Abstract

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.

Proceedings of the National Academy of SciencesVol. 122(16)
Radboud University Nijmegen (NL), University of Freiburg (DE), Utrecht University (NL), Leiden University Medical Center (NL), University Medical Center Freiburg (DE), University Medical Center (US), Radboud University Medical Center (NL), Emma Kinderziekenhuis (NL), Oncode Institute (NL), Institute of Immunology (HR), Medical University of Vienna (AT)
Deutsche Forschungsgemeinschaft, ZonMw, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, KWF Kankerbestrijding, Radboud Universitair Medisch Centrum, European Research Council
Good health and well-being
Openalex Percentile: Top 12%
T-cell and B-cell Immunology
2.39
DOIOpen Access PDFOpenAlex
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