Molecular Mechanisms of B Cell Antigen Gathering and Endocytosis
Generation of high-affinity, protective antibodies requires B cell receptor (BCR) signaling, as well as antigen internalization and presentation to helper T cells. B cell antigen internalization is initiated by antigen capture, either from solution or from immune synapses formed on the surface of antigen-presenting cells, and proceeds via clathrin-dependent endocytosis and intracellular routing to late endosomes. Although the components of this pathway are still being discovered, it has become clear that antigen internalization is actively regulated by BCR signaling at multiple steps and, vice versa, that localization of the BCR along the endocytic pathway modulates signaling. Accordingly, defects in BCR internalization or trafficking contribute to enhanced B cell activation in models of autoimmune diseases and in B cell lymphomas. In this review, we discuss how BCR signaling complexes regulate each of the steps of this endocytic process and why defects along this pathway manifest as hyperactive B cell responses in vivo.
KeywordsActin Polymerization Early Endosome Late Endosome Phosphatidyl Inositol Immune Synapse
The authors’ research has been supported by the UK Medical Research Council (Unit Programme number U117597138) and by the Francis Crick Institute. PT is supported by the EMBO Young Investigator Programme. RH is supported by a Rubicon grant from the Netherlands Organisation for Scientific Research (NWO).
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