期刊
IMMUNOLOGICAL REVIEWS
卷 256, 期 1, 页码 177-189出版社
WILEY-BLACKWELL
DOI: 10.1111/imr.12113
关键词
B cells; B-cell antigen receptor; actin cytoskeleton; signal transduction; endocytosis
类别
资金
- NIH
- Maryland Stem Cell Research Fund
- NSF
- University of Maryland Ann G. Wylie Dissertation Fellowship
- Direct For Mathematical & Physical Scien
- Division Of Physics [1206060] Funding Source: National Science Foundation
Upon recognizing cognate antigen, B cells mobilize multiple cellular apparatuses to propagate an optimal response. Antigen binding is transduced into cytoplasmic signaling events through B-cell antigen receptor (BCR)-based signalosomes at the B-cell surface. BCR signalosomes are dynamic and transient and are subsequently endocytosed for antigen processing. The function of BCR signalosomes is one of the determining factors for the fate of B cells: clonal expansion, anergy, or apoptosis. Accumulating evidence underscores the importance of the actin cytoskeleton in B-cell activation. We have begun to appreciate the role of actin dynamics in regulating BCR-mediated tonic signaling and the formation of BCR signalosomes. Our recent studies reveal an additional function of the actin cytoskeleton in the downregulation of BCR signaling, consequently contributing to the generation and maintenance of B-cell self-tolerance. In this review, we discuss how actin remodels its organization and dynamics in close coordination with BCR signaling and how actin remodeling in turn amplifies the activation and subsequent downregulation process of BCR signaling, providing vital feedback for optimal BCR activation.
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