Abstract
Binding of antigen to the B cell antigen receptor (BCR) triggers signaling that ultimately leads to B cell activation. Using quantitative fluorescence resonance energy transfer imaging, we provide evidence here that the BCR is a monomer on the surface of resting cells. Binding of multivalent antigen clustered the BCR, resulting in the simultaneous phosphorylation of and a conformational change in the BCR cytoplasmic domains from a closed to an open form. Notably, the open conformation required immunoreceptor tyrosine-activation motif and continuous Src family kinase activity but not binding of the kinase Syk. Thus, the initiation of BCR signaling is a very dynamic process accompanied by reversible conformational changes induced by Src family kinase activity.
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Acknowledgements
We thank T. Jin for the initial setup of the imaging system and J. Coligan for help with transfections. Supported by the Intramural Research program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.
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Tolar, P., Sohn, H. & Pierce, S. The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer. Nat Immunol 6, 1168–1176 (2005). https://doi.org/10.1038/ni1262
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DOI: https://doi.org/10.1038/ni1262
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