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and Ig-β) are involved. A B-cell antigen receptor forms a signaling complex consisting of one B-cell receptor bound to one antigenic peptide (figure adapted from Miller, [@CR124]). 4.2 In the mature B cell, a BCR cross-linking leads to signal transduction (figure adapted from Miller, [@CR124]). 4.3 Antigen binding to the BCR leads to the recruitment of phosphatidylinositol-4,5-bisphosphate (PIP2) to the B cell membrane, the activation of phospholipase Cγ (PLCγ), which hydrolyzes PIP2 to produce diacylglycerol (DAG) and inositol (1,4,5) triphosphate (IP3) (figure adapted from Miller, [@CR124]). 4.4 DAG and IP3 release calcium from intracellular stores leading to the activation of protein kinase C (PKC) (figure adapted from Miller, [@CR124]). 4.5 PKC phosphorylates the cytoskeletal proteins (actin and tubulin) and the mitogen-activated protein (MAP) kinases (figure adapted from Miller, [@CR124]). 4.6 MAP kinases in turn lead to the phosphorylation and subsequent activation of transcription factors (e.g. AP-1) which control the expression of genes responsible for B-cell proliferation (figure adapted from Miller, [@CR124]). 4.7 In addition, BCR cross-linking can also lead to the secretion of cytokines (e.g. IL-2, IL-4 and IL-6) (figure adapted from Miller, [@CR124]). 4.8 B cells can also be activated via the B-cell receptor complex and the Fas receptor, or the CD40 receptor complex (Bolton et al. [@CR16]; Cornetta et al. [@CR31]; Devergne et al. [@CR43]; Kabelitz et al. [@CR82]; Teh and Rochlitz [@CR192]). 4.9 Recent data indicate that activation via IgD is also required for B-cell development (Kinjo et al. [@CR94]; Richter et al. [@CR156]). 4.10 The recent

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