Precisely how receptor proteins transduce signals at the cell surface remains an outstanding question in signal transduction. As for other receptors, one proposed mechanism for signaling by the B cell antigen receptor is that ligand-induced dimerization causes receptor dimerization and consequent association and activation of kinases that bind to the receptor. However, new work by Yang and Reth favors a rather different interpretation. The authors used a bifluorescence complementation assay in which receptor subunits are tagged with N-terminal or C-terminal fragments of yellow- and cyan fluorescent proteins so that association of receptor subunits could be monitored by detection of fluorescence by confocal microscopy. The high efficiency of fluorescence indicated that the receptors formed oligomers at the cell surface. However, further experiments with mutant receptors that failed to oligomerize indicated that the oligomers represented an inactive state of the receptor. A non-oligomerizing mutant, on the other hand, was active and could not be stably expressed on cells. Thus, the authors propose that, in resting cells, the B cell receptor is primarily in an oligomeric, autoinhibited state. Antigen binding would then promote a shift to monomer formation. The requirement for polyvalent antigen, previously interpreted to mean that bound receptors would be brought together, might instead reflect the need to restrain the monomers from oligomerizing. This would not require precise placement of the receptor subunits and could thus explain why structurally dissimilar antigens can activate B cell receptors.
J. Yang, M. Reth, Oligomeric organization of the B-cell antigen receptor on resting cells. Nature 467, 465–469 (2010). [PubMed]