The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer

Authors:
Tolar P, Sohn HW and Pierce SK
In:
Source: Nat Immunol
Publication Date: (2005)
Issue: 6(11): 1168-1176
Research Area:
Immunotherapy / Hematology
Cells used in publication:
J558L
Species: mouse
Tissue Origin: blood
Platform:
Nucleofectorâ„¢ I/II/2b
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.