A conformation-induced oligomerization model for B cell receptor microclustering and signaling

Abstract

The B cell receptor (BCR) generates both antigen-independent and dependent intracellular signals that are essential for B cell development and antibody responses against pathogens. However, the molecular mechanisms underlying the initiation of BCR signaling are not understood completely yet. The advent of new imaging technologies is allowing the earliest events in B cell signaling to be viewed both in vivo in lymphoid tissues and in vitro in living cells, in real-time, down to the single molecule level. Here we review recent progress in the use of these technologies to decipher the earliest events that follow B cell antigen recognition. Based on recent data using these techniques, we propose a model for the initiation of BCR signaling in which the binding of antigen induces a conformational change in the BCR's extracellular domains leading to BCR oligomerization and signaling. We conclude that testing this model will require an in-depth understanding of the unique structural and organizational features of the BCR in the plasma membrane of living B cells in the presence and absence of antigen.