B Cell Receptor Signaling: Picky About PI3Ks

The B cell receptor (BCR) and the pre-BCR control cell fate at many stages of B cell development, survival, and antigen response. Most of these processes require the activation of phosphatidylinositol 3-kinase (PI3K). Previous work has pointed to p110 delta as the key catalytic isoform of PI3K for many B cell responses. A study of mice with different combinations of PI3K mutations confirms the central role of p110 delta in agonist-mediated signaling, while identifying an unexpected function for the p110 alpha isoform in tonic signaling by the pre-BCR and mature BCR.