PI3K Signaling in Normal B Cells and Chronic Lymphocytic Leukemia (CLL).
B cells provide immunity to extracellular pathogens by secreting a diverse repertoire of antibodies with high affinity and specificity for exposed antigens. The B cell receptor (BCR) is a transmembrane antibody, which facilitates the clonal selection of B cells producing secreted antibodies of the same specificity. The diverse antibody repertoire is generated by V(D)J recombination of heavy and light chain genes, whereas affinity maturation is mediated by activation-induced cytidine deaminase (AID)-mediated mutagenesis. These processes, which are essential for the generation of adaptive humoral immunity, also render B cells susceptible to chromosomal rearrangements and point mutations that in some cases lead to cancer. In this chapter, we will review the central role of PI3K s in mediating signals from the B cell receptor that not only facilitate the development of functional B cell repertoire, but also support the growth and survival of neoplastic B cells, focusing on chronic lymphocytic leukemia (CLL) B cells. Perhaps because of the central role played by PI3K in BCR signaling, B cell leukemia and lymphomas are the first diseases for which a PI3K inhibitor has been approved for clinical use.
Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, CB22 3AT, UK. klaus.okkenhaug@babraham.ac.uk.
Klaus
K
Okkenhaug
Department of Leukemia, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. jaburger@mdanderson.org.
Jan A
JA
Burger
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D002470:Cell Survival; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases