title: Classical Mus musculus Igκ enhancers support transcription but not high level somatic hypermutation from a V-lambda promoter in chicken DT40 cells.
abstract: Somatic hypermutation (SHM) of immunoglobulin genes is initiated by activation-induced cytidine deaminase (AID) in activated B cells. This process is strictly dependent on transcription. Hence, cis-acting transcriptional control elements have been proposed to target SHM to immunoglobulin loci. The Mus musculus Igκ locus is regulated by the intronic enhancer (iE/MAR) and the 3' enhancer (3'E), and multiple studies using transgenic and knock-out approaches in mice and cell lines have reported somewhat contradictory results about the function of these enhancers in AID-mediated sequence diversification. Here we show that the M. musculus iE/MAR and 3'E elements are active solely as transcriptional enhancer when placed in the context of the IGL locus in Gallus gallus DT40 cells, but they are very inefficient in targeting AID-mediated mutation events to this locus. This suggests that either key components of the cis-regulatory targeting elements reside outside the murine Igκ transcriptional enhancer sequences, or that the targeting of AID activity to Ig loci occurs by largely species-specific mechanisms.
authors.affiliation: Laboratory of Molecular Biology and Immunology, Molecular Immunology Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Naga Rama
authors.initials: NR
authors.lastname: Kothapalli
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Norton
authors.forename: Sebastian D
authors.initials: SD
authors.lastname: Fugmann
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D004742:Enhancer Elements, Genetic; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D007136:Immunoglobulins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: C014609:IgK; D007146:Immunoglobulin lambda-Chains; D007136:Immunoglobulins