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Sci. Signal., 10 August 2010
Vol. 3, Issue 134, p. ra60
[DOI: 10.1126/scisignal.2001104]

RESEARCH ARTICLES

Editor's Summary

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 p110{delta} 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 p110{delta} and p110{alpha} blocked antigen-independent, so-called tonic, BCR signaling, which was required for B cell development. In contrast, antigen-dependent signaling required p110{delta}. As Limon and Fruman discuss in the accompanying Perspective, the discovery of this role for p110{alpha} suggests that the combined inhibition of p110{alpha} and p110{delta}, rather than of p110{delta} alone, would be more effective as a therapy to target B cell malignancies that involve chronic BCR signaling.

Citation: F. Ramadani, D. J. Bolland, F. Garcon, J. L. Emery, B. Vanhaesebroeck, A. E. Corcoran, K. Okkenhaug, The PI3K Isoforms p110{alpha} and p110{delta} Are Essential for Pre–B Cell Receptor Signaling and B Cell Development. Sci. Signal. 3, ra60 (2010).

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