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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:p>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\u2013CD70 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.<\/jats:p>","DOI":"10.1073\/pnas.2414002122","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T11:51:21Z","timestamp":1744717881000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["CD70 recruitment to the immunological synapse is dependent on CD20 in B cells"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6727-3273","authenticated-orcid":false,"given":"Abbey B.","family":"Arp","sequence":"first","affiliation":[{"name":"Department of Medical BioSciences, Radboud Institute for Medical Innovation, Radboud University Medical Center","place":["Nijmegen, The 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