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Immunol Rev. 2010 Sep;237(1):55-71. doi: 10.1111/j.1600-065X.2010.00934.x.

Role of PI3K in the generation and survival of B cells.

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Faculty of Biology, Department of Molecular Immunology, Albert-Ludwigs-Universit├Ąt Freiburg, Freiburg, Germany.


Engagement of the B-cell antigen receptor (BCR) or its precursor, the pre-BCR, induces a cascade of biochemical reactions that regulate the differentiation, selection, survival, and activation of B cells. This cascade is initiated by receptor-associated tyrosine kinases that activate multiple downstream signaling pathways. Since it is required for metabolism, cell growth, development, and survival, the activation of phosphoinositide 3-kinase (PI3K)-dependent pathways represents a crucial event of BCR/pre-BCR signaling. The phosphorylated substrates of the PI3K promote specific recruitment of selected signaling proteins to the plasma membrane, where important signaling complexes are formed to mediate the above-mentioned biological processes. Here, we review the principles of PI3K signaling and highlight the role of an important PI3K-driven module in VDJ recombination of immunoglobulin (Ig) genes during early B-cell development as compared with class switch recombination of Ig genes in mature B cells after activation by specific antigens. Furthermore, we discuss the role of PI3K in the survival of mature B cells, which is strictly dependent on BCR expression and basal BCR signaling.

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