ITAM-mediated tonic signalling through pre-BCR and BCR complexes

Studies carried out over the past few years provide strong support for the idea that Ig alpha-Ig beta-containing complexes such as the pre-B-cell receptor and the B-cell receptor can signal independently of ligand engagement, and this has been termed tonic signalling. In this Review, I discuss recent literature that is relevant to the potential mechanisms by which tonic signals are initiated and regulated, and discuss views on how tonic and ligand-dependent (aggregation-mediated) signalling differ. These mechanisms are relevant to the possibility that tonic signals generated through immunoreceptor tyrosine-based activation motif (ITAM)-containing proteins that are expressed by oncogenic viruses induce transformation in non-haematopoietic cells.