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Nat Rev Immunol. 2010 Nov;10(11):767-77. doi: 10.1038/nri2853. Epub 2010 Oct 11.

The tipping points in the initiation of B cell signalling: how small changes make big differences.

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Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.


B cells are selected by the binding of antigen to clonally distributed B cell receptors (BCRs), triggering signalling cascades that result in B cell activation. With the recent application of high-resolution live-cell imaging, we are gaining an understanding of the events that initiate BCR signalling within seconds of its engagement with antigen. These observations are providing a molecular explanation for fundamental aspects of B cell responses, including antigen affinity discrimination and the value of class switching, as well as insights into the underlying causes of B cell tumorigenesis. Advances in our understanding of the earliest molecular events that follow antigen binding to the BCR may provide a general framework for the initiation of signalling in the adaptive immune system.

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