Journal article
Regulation of AID expression in the immune response
The Journal of experimental medicine, Vol.204(5), pp.1145-1156
05/14/2007
DOI: 10.1084/jem.20061952
PMCID: PMC2118564
PMID: 17452520
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.
Details
- Title: Subtitle
- Regulation of AID expression in the immune response
- Creators
- Elizabeth E Crouch - Genomic Integrity and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Zhiyu Li - Genomic Integrity and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Makiko Takizawa - Genomic Integrity and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Stefan Fichtner-Feigl - Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases (NIAID)Polyxeni Gourzi - Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10021Carolina Montaño - Genomic Integrity and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Lionel Feigenbaum - Laboratory Animal Science Program, Science Applications International Corporation (SAIC), NCI, NIH, Frederick, MD 21702Patrick Wilson - Molecular Immunogenetics, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104Siegfried Janz - Laboratory of Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892F. Nina Papavasiliou - Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10021Rafael Casellas - Genomic Integrity and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.204(5), pp.1145-1156
- DOI
- 10.1084/jem.20061952
- PMID
- 17452520
- PMCID
- PMC2118564
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 05/14/2007
- Academic Unit
- Pathology
- Record Identifier
- 9984083821302771
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