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When B cells are exposed to antigens, they use their B‐cell receptors (BCRs) to transduce this external signal into internal signaling cascades and uptake antigen, which activate transcriptional programs. Signaling activation requires complex cytoskeletal remodeling initiated by BCR signaling. The actin cytoskeletal remodeling drives B‐cell morphological changes, such as spreading, protrusion, contraction, and endocytosis of antigen by mechanical forces, which in turn affect BCR signaling. Therefore, the relationship between the actin cytoskeleton and BCR signaling is a two‐way feedback loop. These morphological changes represent the indirect ways by which the actin cytoskeleton regulates BCR signaling. Recent studies using high spatiotemporal resolution microscopy techniques have revealed that actin also can directly influence BCR signaling. Cortical actin networks directly affect BCR mobility, not only during the resting stage by serving as diffusion barriers, but also at the activation stage by altering BCR diffusivity through enhanced actin flow velocities. Furthermore, the actin cytoskeleton, along with myosin, enables B cells to sense the physical properties of its environment and generate and transmit forces through the BCR. Consequently, the actin cytoskeleton modulates the signaling threshold of BCR to antigenic stimulation. This review discusses the latest research on the relationship between BCR signaling and actin remodeling, and the research techniques. Exploration of the role of actin in BCR signaling will expand fundamental understanding of the relationship between cell signaling and the cytoskeleton and the mechanisms underlying cytoskeleton‐related immune disorders and cancer.
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A hybrid stochastic–deterministic mechanochemical model of cell polarization
Polarization is a crucial component in cell differentiation, development, and motility, but its details are not yet well understood. At the onset of cell locomotion, cells break symmetry to form well-defined cell fronts and rears. This polarity establishment varies across cell types: in Dictyostelium discoideum cells, it is mediated by biochemical signaling pathways and can function in the absence of a cytoskeleton, while in keratocytes, it is tightly connected to cytoskeletal dynamics and mechanics. Theoretical models that have been developed to understand the onset of polarization have explored either signaling or mechanical pathways, yet few have explored mechanochemical mechanisms. However, many motile cells rely on both signaling modules and actin cytoskeleton to break symmetry and achieve a stable polarized state. We propose a general mechanochemical polarization model based on coupling between a stochastic model for the segregation of signaling molecules and a simplified mechanical model for actin cytoskeleton network competition. We find that local linear coupling between minimally nonlinear signaling and cytoskeletal systems, separately not supporting stable polarization, yields a robustly polarized cell state. The model captures the essence of spontaneous polarization of neutrophils, which has been proposed to emerge due to the competition between frontness and backness pathways.
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- PAR ID:
- 10293310
- Editor(s):
- Edelstein-Keshet, Leah
- Date Published:
- Journal Name:
- Molecular Biology of the Cell
- Volume:
- 31
- Issue:
- 15
- ISSN:
- 1059-1524
- Page Range / eLocation ID:
- 1637 to 1649
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1091/mbc.E19-09-0549
