Activation-induced Deaminase (AID)-directed Hypermutation in the Immunoglobulin Sμ Region
Open Access
- 18 February 2002
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 195 (4) , 529-534
- https://doi.org/10.1084/jem.20012144
Abstract
Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in variable regions and large deletions in S regions, respectively. Yet both depend on activation-induced deaminase (AID), the function of which in the two reactions has been an enigma. Here we report that B cell stimulation which induces CSR but not SHM, leads to AID-dependent accumulation of SHM-like point mutations in the switch μ region, uncoupled with CSR. These findings strongly suggest that AID itself or a single molecule generated by RNA editing function of AID may mediate a common step of SHM and CSR, which is likely to be involved in DNA cleavage.Keywords
This publication has 37 references indexed in Scilit:
- Molecular Mechanism of Class Switch Recombination: Linkage with Somatic HypermutationAnnual Review of Immunology, 2002
- AID is required to initiate Nbs1/γ-H2AX focus formation and mutations at sites of class switchingNature, 2001
- Activation-Induced Cytidine Deaminase (AID) Deficiency Causes the Autosomal Recessive Form of the Hyper-IgM Syndrome (HIGM2)Cell, 2000
- Frequent but biased class switch recombination in the Sμ flanking regionsCurrent Biology, 1998
- Specificity in V(D)J recombination: new lessons from biochemistry and geneticsCurrent Opinion in Immunology, 1997
- The SCID but Not the RAG-2 Gene Product Is Required for Sμ–Sε Heavy Chain Class SwitchingImmunity, 1996
- Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targetingCell, 1993
- Molecular characterization of single memory B cellsNature, 1991
- Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responsesCell, 1987
- Switch region of immunoglobulin Cμ gene is composed of simple tandem repetitive sequencesNature, 1981