The actin cytoskeleton coordinates the signal transduction and antigen processing functions of the B cell antigen receptor

Abstract

The B cell antigen receptor (BCR) is the sensor on the B cell surface that surveys foreign molecules (antigen) in our bodies and activates B cells to generate antibody responses upon encountering cognate antigen. The binding of antigen to the BCR induces signaling cascades in the cytoplasm, which provides the first signal for B cell activation. Subsequently, BCRs internalize and target bound antigen to endosomes, where antigen is processed into T cell recognizable forms. T helper cells generate the second activation signal upon binding to antigen presented by B cells. The optimal activation of B cells requires both signals, thereby depending on the coordination of BCR signaling and antigen transport functions. Antigen binding to the BCR also induces rapid remodeling of the cortical actin network of B cells. While being initiated and controlled by BCR signaling, recent studies reveal that this actin remodeling is critical for both the signaling and antigen processing functions of the BCR, indicating a role for actin in coordinating these two pathways. Here we will review previous and recent studies on actin reorganization during BCR activation and BCR-mediated antigen processing, and discuss how actin remodeling translates BCR signaling into rapid antigen uptake and processing while providing positive and negative feedback to BCR signaling.

Keywords: actin cytoskeleton; endocytosis; receptor; signal transduction.

Figure 1

Role of the actin cytoskeleton in coordination of BCR signaling and antigen processing functions. BCR signaling triggers actin reorganization as a series of sequential events. An initial transient detachment and disassembly of the cortical actin network is induced by dephosphorylation ezrin and cofilin (A), and a subsequent polarized actin reassembly is mediated in part by Btk-activated WASP (B). The actin remodeling facilitates BCR self-clustering and signaling induction in BCR microclusters. Actin-driven B cell spreading enhances BCR microclustering and signaling (A-B). The transition of actin-mediated cell spreading to contraction promotes the coalescence of BCR microclusters and the formation of the central cluster, which leads to signaling attenuation (C). B cell contraction also likely helps to gather BCR-antigen complexes into endocytosing vesicles. The continuous actin remodeling, the actin adaptor protein Apb1 that couples F-actin with dynamin, and the actin motor non-muscle myosin II (MyoII) are required for the formation and fission of BCR containing budding vesicles from the plasma membrane (D).