Research ArticleImmunology

The PI3K Isoforms p110α and p110δ Are Essential for Pre–B Cell Receptor Signaling and B Cell Development

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Sci. Signal.  10 Aug 2010:
Vol. 3, Issue 134, pp. ra60
DOI: 10.1126/scisignal.2001104

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Relative Importance

B cell receptor (BCR) signaling drives the development and survival of B cells and their responses to antigens. Members of the phosphatidylinositol 3-kinase (PI3K) family of lipid kinases mediate BCR signaling. Whereas the p110δ isoform of PI3K is necessary for antigen-dependent BCR signaling, its loss does not affect B cell development in the bone marrow. Ramadani et al. found that, whereas deficiency in individual PI3K isoforms in mice did not prevent early B cell development, deficiency in both p110δ and p110α blocked antigen-independent, so-called tonic, BCR signaling, which was required for B cell development. In contrast, antigen-dependent signaling required p110δ. As Limon and Fruman discuss in the accompanying Perspective, the discovery of this role for p110α suggests that the combined inhibition of p110α and p110δ, rather than of p110δ alone, would be more effective as a therapy to target B cell malignancies that involve chronic BCR signaling.