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<p>CD20 is a four-helix transmembrane protein specifically expressed in B-cells that serves as a prominent target of therapeutic anti-CD20 antibodies. It is localized in a membrane nanocluster harboring the B-cell antigen receptor of IgD class (IgD-BCR), where it functions to maintain the resting state of naïve B-lymphocytes. How CD20 exerts this resting B-cell gatekeeper function is not yet known. Using Ramos and human peripheral blood B-cells, we show here that the serine/threonine kinase PKCδ constitutively phosphorylates serine residues in the two cytosolic tails of CD20. Phosphorylated CD20 becomes a binding target for 14-3-3 adaptor proteins, which link it to the RhoA GDP/GTP exchange factor GEF-H1 and the microtubule network, supporting the function of the IgD-BCR nanocluster. Binding of anti-CD20 antibodies results in microtubule dissociation and replacement of the GEF-H1/CD20 complex with a RhoA-GTP/ROCK1/CD20 complex, which promotes actomyosin contractility. Our study suggests that CD20 not only maintains the resting state of B-lymphocytes by anchoring the microtubule network and controlling the stability of the IgD-BCR nanocluster, but also mediates the microtubule/actin switch in active B-lymphocytes. These findings could have important implications for anti-CD20 antibody treatment and the optimization of therapeutic protocols.</p>

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CD20 tails interact with the 14-3-3/GEF-H1 complex and microtubule network upon PKCδ phosphorylation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Kathrin Kläsener,
  • Cindy Eunhee Lee,
  • Julian Bender,
  • Angela Naumann,
  • Lena Reimann,
  • Geoffroy Andrieux,
  • Claudio Mussolino,
  • Nadja Herrmann,
  • Roland Nitschke,
  • Reinhard E Voll,
  • Bettina Warscheid,
  • Klaus Warnatz,
  • Michael Reth

摘要

CD20 is a four-helix transmembrane protein specifically expressed in B-cells that serves as a prominent target of therapeutic anti-CD20 antibodies. It is localized in a membrane nanocluster harboring the B-cell antigen receptor of IgD class (IgD-BCR), where it functions to maintain the resting state of naïve B-lymphocytes. How CD20 exerts this resting B-cell gatekeeper function is not yet known. Using Ramos and human peripheral blood B-cells, we show here that the serine/threonine kinase PKCδ constitutively phosphorylates serine residues in the two cytosolic tails of CD20. Phosphorylated CD20 becomes a binding target for 14-3-3 adaptor proteins, which link it to the RhoA GDP/GTP exchange factor GEF-H1 and the microtubule network, supporting the function of the IgD-BCR nanocluster. Binding of anti-CD20 antibodies results in microtubule dissociation and replacement of the GEF-H1/CD20 complex with a RhoA-GTP/ROCK1/CD20 complex, which promotes actomyosin contractility. Our study suggests that CD20 not only maintains the resting state of B-lymphocytes by anchoring the microtubule network and controlling the stability of the IgD-BCR nanocluster, but also mediates the microtubule/actin switch in active B-lymphocytes. These findings could have important implications for anti-CD20 antibody treatment and the optimization of therapeutic protocols.