Regulation of aicda expression and AID activity: relevance to somatic hypermutation and class switch DNA recombination

Critical Reviews in Immunology
Zhenming XuPaolo Casali

Abstract

Expression and activity of activation-induced cytidine deaminase (AID) encoded by the aicda gene are essential for immunoglobulin (Ig) gene somatic hypermutation (SHM) and class switch DNA recombination (CSR). SHM and CSR unfold, in general, in germinal centers and/are central to the maturation of effective antibody responses. AID expression is induced by activated B-cell CD40 signaling, which is critical for the germinal center reaction, and is further enhanced by other stimuli, including interleukin-4 (IL-4) secreted from CD4+ T cells or Toll-like receptor (TLR)-activating bacterial and/or viral molecules. Integration of different intracellular signal transduction pathways, as activated by these stimuli, leads to a dynamic aicda-regulating program, which involves both positively acting trans-factors, such as Pax5, HoxC4, E47, and Irf8, and negative modulators, such as Blimp1 and Id2, to restrict aicda expression primarily to germinal center B cells. The phosphatidylinositol 3-kinase (PI 3-K), which functions downstream of activated B-cell receptor (BCR) signaling, likely plays an important role in triggering the downregulation of aicda expression in postgerminal center B cells and throughout plasmacytoid differentiation. In B...Continue Reading

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Citations

Apr 25, 2012·Cancer Immunology, Immunotherapy : CII·Diana MechtcheriakovaErika Jensen-Jarolim
Jun 26, 2012·Nature Reviews. Immunology·Zhenming XuPaolo Casali
Aug 24, 2010·Nature Structural & Molecular Biology·Zhenming XuPaolo Casali
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