Xid-like Phenotypes: A B Cell Signalosome Takes Shape

Abstract

The molecular events linking BCR stimulation to Ca2+ flux are coming into focus. Considering together the results of biochemical studies and mouse genetic analyses, strong support now exists for a “signalosome” model of B cell activation. In this view, the central response regulator (PLCγ2) is activated by multiple independent inputs that are organized by interactions with membrane phosphoinositides and a docking protein (BLNK). A further level of organization may be provided by localization in lipid rafts. It should be emphasized that the picture of the B cell signalosome is probably incomplete. It is likely that other proteins that interact with Btk may be involved in signal integration and modification. It will be important to apply genetic tests of function to these components. Another challenge for the future is to determine whether distinct signalosomes are organized by other receptors on B cells. The application of gene targeting technology, including conditional inactivation and RAG chimeric approaches, should continue to clarify the complexities of lymphocyte activation.§To whom correspondence should be addressed (e-mail: owenw@microbio.ucla.edu).