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

Nat Immunol. 2005 Nov;6(11):1168-76. doi: 10.1038/ni1262. Epub 2005 Oct 2.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens / immunology
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology*
  • Enzyme Precursors / metabolism
  • Fluorescence Resonance Energy Transfer
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, B-Cell / chemistry*
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction / immunology
  • Syk Kinase
  • src-Family Kinases / metabolism*


  • Antigens
  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, B-Cell
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse
  • src-Family Kinases