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Publication : The constant region of the membrane immunoglobulin mediates B cell-receptor clustering and signaling in response to membrane antigens.

First Author  Tolar P Year  2009
Journal  Immunity Volume  30
Issue  1 Pages  44-55
PubMed ID  19135393 Mgi Jnum  J:143722
Mgi Id  MGI:3828871 Doi  10.1016/j.immuni.2008.11.007
Citation  Tolar P, et al. (2009) The constant region of the membrane immunoglobulin mediates B cell-receptor clustering and signaling in response to membrane antigens. Immunity 30(1):44-55
abstractText  B cells are activated in vivo after the B cell receptors (BCRs) bind to antigens captured on the surfaces of antigen-presenting cells. Antigen binding results in BCR microclustering and signaling; however, the molecular nature of the signaling-active BCR clusters is not well understood. Using single-molecule imaging techniques, we provide evidence that within microclusters, the binding of monovalent membrane antigens results in the assembly of immobile signaling-active BCR oligomers. The oligomerization depends on interactions between the membrane-proximal Cmicro4 domains of the membrane immunoglobulin that are both necessary and sufficient for assembly. Antigen-bound BCRs that lacked the Cmicro4 domain failed to cluster and signal, and conversely, Cmicro4 domains alone clustered spontaneously and activated B cells. These results support a unique mechanism for the initiation of BCR signaling in which antigen binding induces a conformational change in the Fc portion of the BCR, revealing an interface that promotes BCR clustering.
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