Foxos around make B cells tolerable

Rowh, Marta; Bassing, Craig H.

doi:10.1038/ni0608-586

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…Interestingly, the B cell identity-related TFs Pax5 and IKZF1 limit glucose uptake in normal B cells and thereby support a metabolic program that leads to metabolic exhaustion when an oncogene, such as Bcr-Abl, is activated [61]. IL-7 activates the phosphatidyl-inositol-3-kinase (PI3K) pathway, leading to the activation of extracellular regulated kinase (Erk) [62] and Akt and the inactivation of Foxo1 [15,63,64]. The early pre-BCR signal also engages the PI3K cascade via Syk.…”

Section: Signalling Pathways Linking Membrane Receptor Signals To mentioning

confidence: 99%

Regulation of Energy Metabolism during Early B Lymphocyte Development

Urbanczyk

Stein

Schuh

et al. 2018

IJMS

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The most important feature of humoral immunity is the adaptation of the diversity of newly generated B cell receptors, that is, the antigen receptor repertoire, to the body’s own and foreign structures. This includes the transient propagation of B progenitor cells and B cells, which possess receptors that are positively selected via anabolic signalling pathways under highly competitive conditions. The metabolic regulation of early B-cell development thus has important consequences for the expansion of normal or malignant pre-B cell clones. In addition, cellular senescence programs based on the expression of B cell identity factors, such as Pax5, act to prevent excessive proliferation and cellular deviation. Here, we review the basic mechanisms underlying the regulation of glycolysis and oxidative phosphorylation during early B cell development in bone marrow. We focus on the regulation of glycolysis and mitochondrial oxidative phosphorylation at the transition from non-transformed pro- to pre-B cells and discuss some ongoing issues. We introduce Swiprosin-2/EFhd1 as a potential regulator of glycolysis in pro-B cells that has also been linked to Ca2+-mediated mitoflashes. Mitoflashes are bioenergetic mitochondrial events that control mitochondrial metabolism and signalling in both healthy and disease states. We discuss how Ca2+ fluctuations in pro- and pre-B cells may translate into mitoflashes in early B cells and speculate about the consequences of these changes.

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