Abo Bibliothek: Guest
Digitales Portal Digitale Bibliothek eBooks Zeitschriften Referenzen und Berichte Forschungssammlungen
Critical Reviews™ in Immunology
Impact-faktor: 1.352 5-jähriger Impact-Faktor: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Druckformat: 1040-8401
ISSN Online: 2162-6472

Volumes:
Volumen 39, 2019 Volumen 38, 2018 Volumen 37, 2017 Volumen 36, 2016 Volumen 35, 2015 Volumen 34, 2014 Volumen 33, 2013 Volumen 32, 2012 Volumen 31, 2011 Volumen 30, 2010 Volumen 29, 2009 Volumen 28, 2008 Volumen 27, 2007 Volumen 26, 2006 Volumen 25, 2005 Volumen 24, 2004 Volumen 23, 2003 Volumen 22, 2002 Volumen 21, 2001 Volumen 20, 2000 Volumen 19, 1999 Volumen 18, 1998 Volumen 17, 1997 Volumen 16, 1996 Volumen 15, 1995 Volumen 14, 1994

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v27.i4.60
pages 367-397

Regulation of aicda Expression and AID Activity: Relevance to Somatic Hypermutation and Class Switch DNA Recombination

Zhenming Xu
Institute for Immunology, School of Medicine and School of Biological Sciences, University of California, Irvine, CA 92697-4120, USA
Egest J. Pone
Institute for Immunology, School of Medicine and School of Biological Sciences, University of California, Irvine, CA 92697-4120, USA
Ahmed Al-Qahtani
Institute for Immunology, School of Medicine and School of Biological Sciences, University of California, Irvine, CA 92697-4120, USA
Seok-Rae Park
Center for Immunology, School of Medicine and School of Biological Sciences, University of California, Irvine, CA 92697-4120, USA
Hong Zan
Institute for Immunology, School of Medicine and School of Biological Sciences, University of California, Irvine, CA 92697-4120, USA
Paolo Casali
Department of Microbiology and Immunology, School of Medicine University of Texas Health Science Center, 7703 Floyd Curl Drive San Antonio, Texas 78229, USA

ABSTRAKT

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 cells undergoing SHM and CSR, AID activity, and, possibly, AID targeting to the Ig locus are regulated at a posttranslational level, including AID dimerization/oligomerization, nuclear/cytoplasmic AID translocation, and phosphorylation of the AID Ser38 residue by protein kinase A (PKA). Here, we discuss the role of B-cell activation signals, transcription regulation programs, and posttranslational modifications in controlling aicda expression and AID activity, thereby delineating an integrated model of modulation of SHM and CSR in the germinal center reaction.