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Although antigen\u2010induced signaling has been studied extensively, the role of cortical F\u2010actin in antigen\u2010independent tonic BCR signaling is less well understood. Because these signals are essential for the survival of B cells and are consequently exploited by several B\u2010cell lymphomas, we assessed how the cortical F\u2010actin structure influences tonic BCR signal transduction. We employed genetic variants of a primary cell\u2010like B\u2010cell line that can be rendered quiescent to show that cross\u2010linking of actin filaments by \u03b1\u2010actinin\u20104 (ACTN4), but not ACTN1, is required to preserve the dense architecture of F\u2010actin in the cortical area of B cells. The reduced cortical F\u2010actin density in the absence of ACTN4 resulted in increased lateral BCR diffusion. Surprisingly, this was associated with reduced tonic activation of BCR\u2010proximal effector proteins, extracellular signal\u2010regulated kinase, and pro\u2010survival pathways. Accordingly, ACTN4\u2010deficient B\u2010cell lines and primary human B cells exhibit augmented apoptosis. Hence, our findings reveal that cortical F\u2010actin architecture regulates antigen\u2010independent tonic BCR survival signals in human B cells.<\/jats:p>","DOI":"10.1002\/eji.202350774","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T05:40:13Z","timestamp":1706766013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Actinin\u20104 controls survival signaling in B cells by limiting the lateral mobility of B\u2010cell antigen receptors"],"prefix":"10.1002","volume":"54","author":[{"given":"Saed","family":"Alsouri","sequence":"first","affiliation":[{"name":"Institute for Cellular and Molecular Immunology University Medical Center Goettingen  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Ambrose","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of British Columbia  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