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Authors: Robbert Hoogeboom Pavel Tolar
Publish Date: 2015
Volume: , Issue: , Pages: 45-63
Abstract
Generation of highaffinity 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 antigenpresenting cells and proceeds via clathrindependent 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 vivoThe 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 NWOOpen Access This chapter is licensed under the terms of the Creative Commons Attribution 40 International License http//creativecommonsorg/licenses/by/40/ which permits use sharing adaptation distribution and reproduction in any medium or format as long as you give appropriate credit to the original authors and the source provide a link to the Creative Commons licence and indicate if changes were madeThe images or other third party material in this chapter are included in the chapter’s Creative Commons licence unless indicated otherwise in a credit line to the material If material is not included in the chapter’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use you will need to obtain permission directly from the copyright holder
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