Class-Switch Recombination (CSR)/Hyper-IgM (HIGM) Syndromes and Phosphoinositide 3-Kinase (PI3K) Defects

Hyper-IgM syndromes: a model for studying the regulation of class switch recombination and somatic hypermutation generation.

Several genetic defects in class switch recombination, which lead to a hyper-IgM syndrome, have been described recently in humans. In addition to the well known role of CD40-ligand-CD40 interaction, these pathologies demonstrate definitively the requirement of CD40-mediated nuclear factor kappa B activation and the essential role of a recently described molecule, the activation-induced cytidine...

Phosphoinositide 3-kinase and Forkhead, a switch for cell division.

Cell cycle progression is a tightly controlled process. To initiate cell division, mitogens trigger a number of early signals that promote the G(0)-G(1) transition by inducing cell growth and the activation of G(1) cyclins. Activation of cyclin E/cdk2 (cyclin-dependent kinase 2) at the end of G(1) is then required to trigger DNA synthesis (S phase entry). Among the early signals induced by mito...

Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling.

Insulin plays a key role in regulating a wide range of cellular processes. However, until recently little was known about the signalling pathways that are involved in linking the insulin receptor with downstream responses. It is now apparent that the activation of class 1a phosphoinositide 3-kinase (PI 3-kinase) is necessary and in some cases sufficient to elicit many of insulin's effects on gl...

Interallelic Class Switch Recombination

Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling.

Class-switch recombination (CSR) is essential for humoral immunity. However, the regulation of CSR is not completely understood. Here we demonstrate that phosphatidylinositol 3-kinase (PI3K) actively suppressed the onset and frequency of CSR in primary B cells. Consistently, mice lacking the lipid phosphatase, PTEN, in B cells exhibited a hyper-IgM condition due to impaired CSR, which could be ...