AID-mediated diversification within the IgL locus of chicken DT40 cells is restricted to the transcribed IgL gene.
Somatic hypermutation (SHM) and gene conversion (GCV) are closely related processes that increase the diversity the primary immunoglobulin repertoire. In both processes the activation-induced cytidine deaminase (AID) converts cytosine residues to uracils within the DNA of the immunoglobulin (Ig) genes in a transcription-dependent manner, and subsequent error-prone repair processes lead to changes in the antigen recognition site of the encoded receptors. This activity is specifically recruited to the Ig loci by unknown mechanisms. Our analyses of the chicken B-cell line DT40, and derivatives thereof, now revealed that even the closest neighbors of the Ig light chain (IgL) gene are protected from AID activity, albeit being transcribed and thus acting as potential targets of AID. Our findings are in support of a model in which cis-acting DNA boundary elements restrict AID activity to the IgL locus and guard the genome in the vicinity of the IgL gene from deleterious mutations.
Gopal
Anjali R
AR
Molecular Immunology Unit, Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Fugmann
Sebastian D
SD
D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D002645:Chickens / Q000235:genetics* / Q000276:immunology*; D003564:Cytidine Deaminase / Q000378:metabolism*; D004252:DNA Mutational Analysis; D014644:Genetic Variation; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D011110:Polymorphism, Genetic; D054420:Pre-B Cell Receptors / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D002352:Carrier Proteins; D007147:Immunoglobulin Light Chains; D054420:Pre-B Cell Receptors; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase