Diverse stimuli converge on PI3Kδ in B cells.

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Diverse stimuli converge on PI3Kδ in B cells. Diverse stimuli converge on PI3Kδ in B cells. The B-cell receptor (BCR) for antigen, the B-cell coreceptor (CD19, part of a complex with CD21 and CD81), and Toll-like receptors for pathogen-associated molecular patterns all activate PI3Kδ. Cytokines derived from lymphoid stromal cells (BAFF) and T cells (IL-4, TNF-α) also activate PI3Kδ. Chemokines, which signal through GPCRs to PI3Kβ and PI3Kγ in most other cell types, activate PI3Kδ in B cells. The key outputs of PI3Kδ activity for B-cell proliferation and survival are shown below the red arrows. PI3K, phosphoinositide 3-kinase; IL-4, interleukin-4; TNF-α, tumor necrosis factor-α; GPCR, G-protein–coupled receptors. David A. Fruman, and Christian Rommel Cancer Discovery 2011;1:562-572 ©2011 by American Association for Cancer Research