Activation-induced deaminase-mediated class switch recombination is blocked by anti-IgM signaling in a phosphatidylinositol 3-kinase-dependent fashion
نویسندگان
چکیده
منابع مشابه
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 ...
متن کاملDe novo protein synthesis is required for activation-induced cytidine deaminase-dependent DNA cleavage in immunoglobulin class switch recombination.
Activation-induced cytidine deaminase is required for the DNA cleavage step of Ig class switch recombination (CSR). However, its molecular mechanism is controversial. RNA-editing hypothesis postulates that activation-induced cytidine deaminase deaminates cytosine in an unknown mRNA to generate a new mRNA encoding an endonuclease for CSR and thus predicts that DNA cleavage depends on de novo pro...
متن کاملClass Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme
Induced overexpression of AID in CH12F3-2 B lymphoma cells augmented class switching from IgM to IgA without cytokine stimulation. AID deficiency caused a complete defect in class switching and showed a hyper-IgM phenotype with enlarged germinal centers containing strongly activated B cells before or after immunization. AID-/- spleen cells stimulated in vitro with LPS and cytokines failed to un...
متن کاملEvolution of class switch recombination function in fish activation-induced cytidine deaminase, AID.
Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies. Activation-induced cytidine deaminase (AID) is the only known B cell-specific protein required for inducing CSR and SHM in mammals. Lower vertebrates have an AID homologue, and there is some evidence o...
متن کاملATM increases activation-induced cytidine deaminase activity at downstream S regions during class-switch recombination.
Activation-induced cytidine deaminase (AID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the IgH C region and improved Ab effector function. During CSR, AID instigates DNA double-strand break (DSB) formation in switch (S) regions located upstream of C region genes. DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromosomal t...
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ژورنال
عنوان ژورنال: Molecular Immunology
سال: 2008
ISSN: 0161-5890
DOI: 10.1016/j.molimm.2007.09.020