The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer.
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.
Tolar
Pavel
P
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Sohn
Hae Won
HW
Pierce
Susan K
SK
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D004792:Enzyme Precursors / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism*
D000941:Antigens; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases