Role of PI3K in the generation and survival of B cells.
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.
Werner
Markus
M
Faculty of Biology, Department of Molecular Immunology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Hobeika
Elias
E
Jumaa
Hassan
H
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002470:Cell Survival; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction
D019869:Phosphatidylinositol 3-Kinases