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Viewing the antigen‐induced initiation of B‐cell activation in living cells
Author(s) -
Tolar Pavel,
Won Sohn Hae,
Pierce Susan K.
Publication year - 2008
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2008.00583.x
Subject(s) - breakpoint cluster region , b cell receptor , biology , microbiology and biotechnology , antigen , receptor , signal transduction , cell , b cell , cell signaling , immunology , genetics , antibody
Summary: The binding of antigen to the B‐cell receptor (BCR) induces BCR clustering and signaling cascades that lead to the activation of a variety of genes associated with B‐cell activation. Over the last several years, our understanding of the molecular details of the BCR signaling pathways have been considerably advanced; what remains only poorly understood are the molecular events that initiate BCR clustering and how clustering leads to activation. Here, we review our progress using live cell imaging technologies to view the earliest events that follow the B cell's binding of antigen. We provide a model for BCR clustering and B‐cell activation that involves an intrinsic tendency of the BCR to cluster and does not require direct crosslinking of the BCR by multivalent antigens. We suggest that local membrane topology and lipid composition play key roles in BCR clustering and initiation of signaling. We believe that our model for B‐cell activation, in which receptor interactions with monovalent antigens on membrane surfaces lead to receptor clustering, may be highly relevant to the mechanisms by which other immune receptors cluster including the T‐cell receptor in response to monovalent peptide–major histocompatibility complex complexes.