B Cell Receptor Signaling by Tomohiro Kurosaki, Jürgen Wienands

By Tomohiro Kurosaki, Jürgen Wienands

This quantity info our present figuring out of the structure and signaling features of the B mobile antigen receptor (BCR) in healthiness and disorder. the 1st chapters evaluate new insights into the meeting of BCR parts and their association at the cellphone floor. next contributions specialize in the molecular interactions that attach the BCR with significant intracellular signaling pathways akin to Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton’s Tyrosine Kinase and MAP kinases. those components orchestrate cytoplasmic and nuclear responses in addition to cytoskeleton dynamics for antigen internalization. additionally, a key mechanism of ways B cells have in mind their cognate antigen is mentioned intimately. Altogether, the discoveries provided supply a greater figuring out of B mobile biology and aid to provide an explanation for a few B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cellphone tumors, whereas additionally paving the way in which for finally fighting those diseases.

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However, as already discussed, it is rather difficult from studies of the diffusion behavior of receptors with a light microscope to come to valid conclusion about the nanoscale organization of receptors. With the emergence of superresolution microscopy, it is now possible to reach such optical resolution, beyond the diffraction barrier with fluorescence labeled proteins (Huang et al. 2010). Mattila et al. (2013) have used this method to study the BCR organization in primary cells. In line with our finding, both IgD-BCR and IgM-BCR were found to be mostly organized as preformed nanoclusters in resting B cells.

The Resting BCR and Models of Its Activation ................................................................ 1 The Monomeric BCR and the CLM .......................................................................... 2 The Monomeric BCR and the Conformation-Induced Oligomerization Model........ 3 The Higher Organization of the Lymphocyte Membrane.......................................... 4 The Oligomeric BCR and the DAM Hypothesis ....................................................... References ..................................................................................................................................

More recently, the development of the high-speed SPT technique and the tracking of the lateral movement of a single labeled target with a temporal resolution of 25 μs have challenged the notion of freely diffusing proteins in the lipid bilayer (Fujiwara et al. 2002). These studies on fibroblasts showed a partitioning of membrane proteins into submicron compartments which limits their free diffusion and only rarely allows “hopping” between compartments (Kusumi et al. 2005). ” This view is supported by experiments showing that small drug inhibitors of the cytoskeleton alter the diffusion behavior of membrane proteins (Andrews et al.

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