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Regulation of AID expression in the immune response. J Exp Med 2007 May 14;204(5):1145-56

Date

04/25/2007

Pubmed ID

17452520

Pubmed Central ID

PMC2118564

DOI

10.1084/jem.20061952

Scopus ID

2-s2.0-34249108271   184 Citations

Abstract

The B cell-specific enzyme activation-induced cytidine deaminase (AID) has been shown to be essential for isotype switching and affinity maturation of antibody genes during the immune response. Conversely, AID activity has also been linked to autoimmunity and tumorigenesis. Determining how AID expression is regulated in vivo is therefore central to understanding its role in health and disease. Here we use phylogenetic footprinting and high-resolution histone acetylation mapping to accurately demarcate AID gene regulatory boundaries. Based on this strategy, we identify a novel, positive regulatory element required for AID transcription. Furthermore, we generate two AID indicator mouse strains using bacterial artificial chromosomes that faithfully recapitulate endogenous AID expression. The first strain uses a green fluorescent protein reporter to identify B cells that actively express AID during the immune response. In the second strain, AID transcription affects the permanent expression of a yellow fluorescent protein reporter in post-germinal center and terminally differentiated lymphocytes. We demonstrate the usefulness of these novel strains by resolving recent contradictory observations on AID expression during B cell ontogeny.

Author List

Crouch EE, Li Z, Takizawa M, Fichtner-Feigl S, Gourzi P, MontaƱo C, Feigenbaum L, Wilson P, Janz S, Papavasiliou FN, Casellas R

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylation
Animals
B-Lymphocytes
Base Sequence
Chromosomes, Artificial, Bacterial
Cytidine Deaminase
DNA Footprinting
DNA Mutational Analysis
DNA Primers
Deoxyribonuclease I
Flow Cytometry
Gene Expression Regulation
Histones
Immunity, Cellular
Mice
Mice, Transgenic
Microscopy, Fluorescence
Molecular Sequence Data
Phylogeny
Regulatory Elements, Transcriptional
Reverse Transcriptase Polymerase Chain Reaction