The constant region of the membrane immunoglobulin mediates B cell-receptor clustering and signaling in response to membrane antigens

Immunity. 2009 Jan 16;30(1):44-55. doi: 10.1016/j.immuni.2008.11.007.


B cells are activated in vivo after the B cell receptors (BCRs) bind to antigens captured on the surfaces of antigen-presenting cells. Antigen binding results in BCR microclustering and signaling; however, the molecular nature of the signaling-active BCR clusters is not well understood. Using single-molecule imaging techniques, we provide evidence that within microclusters, the binding of monovalent membrane antigens results in the assembly of immobile signaling-active BCR oligomers. The oligomerization depends on interactions between the membrane-proximal Cmicro4 domains of the membrane immunoglobulin that are both necessary and sufficient for assembly. Antigen-bound BCRs that lacked the Cmicro4 domain failed to cluster and signal, and conversely, Cmicro4 domains alone clustered spontaneously and activated B cells. These results support a unique mechanism for the initiation of BCR signaling in which antigen binding induces a conformational change in the Fc portion of the BCR, revealing an interface that promotes BCR clustering.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Membrane / physiology*
  • Immunoglobulin Constant Regions / physiology*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nitrohydroxyiodophenylacetate / metabolism*
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, B-Cell / physiology*
  • Signal Transduction
  • Syk Kinase


  • Immunoglobulin Constant Regions
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, B-Cell
  • Intercellular Adhesion Molecule-1
  • Nitrohydroxyiodophenylacetate
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse