The B cell receptor (BCR) interacts with foreign antigens to mediate B cell activation and secretion of antibodies. B cell activation begins with initiation of signaling pathways, such as NFAT, NF-κB, and MAPK, and endocytosis of the BCR-antigen complex. Many studies have investigated the signaling pathways associated with BCR activation, and this work has led to significant advances in drug therapies to treat cancer and autoimmune diseases that are linked to aberrant BCR signaling. Less is known, however, about the mechanisms of BCR endocytosis and the role endocytosis plays in B cell pathogenesis. This chapter will review key characteristics of the BCR, including a review of signaling pathways, and endocytic mechanisms associated with the activated BCR. We will also review recent studies investigating the role of BCR endocytosis disease pathogenesis.
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B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor.
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- BCAP (B cell adapter for PI 3-kinase) plays a critical role in B cell signaling, particularly in response to viral particles, but its specific function in antibody production was unclear.
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B cells rapidly adapt their endocytic pathway to promote the uptake and processing of extracellular antigens recognized through the B-cell receptor (BCR). The mechanisms coupling changes in endomembrane trafficking to the capacity of B cells to screen for antigens within lymphoid tissues remain unaddressed. We investigated the role of SNX5, a member of the sorting nexin family, which interacts with endocytic membranes to regulate vesicular trafficking and macropinocytosis.
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