Abstract
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 Cμ4 domains of the membrane immunoglobulin that are both necessary and sufficient for assembly. Antigen-bound BCRs that lacked the Cμ4 domain failed to cluster and signal, and conversely, Cμ4 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 44-55 |
| Number of pages | 12 |
| Journal | Immunity |
| Volume | 30 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 16 2009 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank M. Davis and J. Huppa for advice on bilayer preparation, T. Meckel for advice on single-molecule data analysis, C.-Y. Huang for advice on statistical analysis, and J. Brzostowski for help with imaging and comments on the manuscript. This work has been supported by the Intramural Research program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.
Keywords
- MOLIMMUN
