B cell antigen receptor signaling and internalization are mutually exclusive events

PLoS Biol. 2006 Jul;4(7):e200. doi: 10.1371/journal.pbio.0040200.


Engagement of the B cell antigen receptor initiates two concurrent processes, signaling and receptor internalization. While both are required for normal humoral immune responses, the relationship between these two processes is unknown. Herein, we demonstrate that following receptor ligation, a small subpopulation of B cell antigen receptors are inductively phosphorylated and selectively retained at the cell surface where they can serve as scaffolds for the assembly of signaling molecules. In contrast, the larger population of non-phosphorylated receptors is rapidly endocytosed. Each receptor can undergo only one of two mutually exclusive fates because the tyrosine-based motifs that mediate signaling when phosphorylated mediate internalization when not phosphorylated. Mathematical modeling indicates that the observed competition between receptor phosphorylation and internalization enhances signaling responses to low avidity ligands.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Cell Membrane / immunology
  • Endocytosis*
  • Humans
  • Immunoglobulin alpha-Chains / chemistry
  • Immunoglobulin alpha-Chains / metabolism
  • Models, Biological
  • Monophenol Monooxygenase / metabolism
  • Phosphorylation
  • Receptors, Antigen, B-Cell / chemistry
  • Receptors, Antigen, B-Cell / metabolism*
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Signal Transduction*


  • Immunoglobulin alpha-Chains
  • Receptors, Antigen, B-Cell
  • Monophenol Monooxygenase
  • Receptors, Platelet-Derived Growth Factor