The cytoskeletal control of B cell receptor and integrin signaling in normal B cells and chronic lymphocytic leukemia.

B cells migrate within lymphoid organs during maturation and activation, processes orchestrated by the interplay between B cell receptor (BCR) signaling and microenvironmental cues. Integrins act as mechanoreceptors, linking BCR activation to cytoskeletal remodeling, facilitating immune synapse formation, antigen recognition, and extraction. BCR activation models describe receptor clustering and mechanical changes within the antigen-BCR complex. Upon activation, immune synapses form, enabling antigen extraction and downstream signaling. Integrins stabilize these synapses, amplify BCR signaling, and modulate BCR positioning via actin reorganization. In chronic lymphocytic leukemia (CLL), aberrant BCR signaling and integrins are major players in leukemic cell homing, prognosis, and therapy resistance. In this review, we summarize the current understanding of the interplay of BCR mechanics and B cell localization, with a particular focus on communication between BCR signaling and integrin-mediated processes via actin dynamics. We give insights into normal B cell biology and then outline aspects typical to CLL.