BCR-induced actin rearrangement provides a driving force for the formation of surface BCR signalosomes (84.1)

Abstract

In response to antigens, the BCR forms surface signalosomes where it initiates signaling cascades and antigen internalization. This study examines the role of the actin cytoskeleton in BCR signalosome formation. Both multi-valent soluble and membrane-associated antigens induce BCR clustering and actin reorganization. Actin is actively polymerized at BCR microclusters upon their formation and surrounding BCR clusters as they are merged into central clusters. Actin regulators, WASP, cofilin and gelsolin, are activated and recruited to BCR clusters. Latrunculin or jasplakinolide treatment, which blocks BCR-induced actin reorganization by depolymerizing or stabilizing F-actin, inhibits surface BCR clustering and B cell spreading. Jasplakinolide blocks antigen-triggered tyrosine phosphorylation. In contract, latrunculin alone, in the absence of antigenic stimulation, induces BCR microclustering and tyrosine phosphorylation, however, in a much slower kinetics than those induced by antigens. Btk deficiency inhibits not only antigen-induced actin polymerization, but also antigen-induced B cell spreading and BCR clustering. These results indicate that BCR-induced, Btk-dependent actin reorganization, consisting of temporospatially regulated actin polymerization and depolymerization, promotes the formation of surface BCR signalosomes by increasing the speed and the extend of BCR engagement and clustering. Our study reveals an actin-mediated positive feedback mechanism for BCR signaling.