Surface protein CD20 serves as the critical target of immunotherapy in various B-cell malignancies for decades, however its biological function and regulation remain largely elusive. Better understanding of CD20 function may help to design improved rational therapies to prevent development of resistance. Using CRISPR/Cas9 technique, we have abrogated CD20 expression in five different malignant B-cell lines. We show that CD20 deletion has no effect upon B-cell receptor signaling or calcium flux. Also B-cell survival and proliferation is unaffected in the absence of CD20. On the contrary, we found a strong defect in actin cytoskeleton polymerization and, consequently, defective cell adhesion and migration in response to homeostatic chemokines SDF1α, CCL19 and CCL21. Mechanistically, we could identify a reduction in chemokine-triggered PYK2 activation, a calcium-activated signaling protein involved in activation of MAP kinases and cytoskeleton regulation. These cellular defects in consequence result in a severely disturbed homing of B cells in vivo.

• MeSH
• aktiny metabolismus   MeSH
• antigeny CD20 genetika   metabolismus   fyziologie   MeSH
• B-buněčný lymfom metabolismus   patologie   MeSH
• B-lymfocyty patologie   fyziologie   MeSH
• buněčná adheze fyziologie   MeSH
• genový knockdown MeSH
• leukemie B-buněčná metabolismus   patologie   MeSH
• lidé MeSH
• multimerizace proteinu fyziologie   MeSH
• myši inbrední NOD MeSH
• myši SCID MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• pohyb buněk fyziologie   MeSH
• polymerizace MeSH
• receptory antigenů B-buněk metabolismus   MeSH
• signální transdukce imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH