AID-mediated diversification within the IgL locus of chicken DT40 cells is restricted to the transcribed IgL gene

Anjali R. Gopal; Sebastian D. Fugmann

doi:10.1016/j.molimm.2007.10.017

AID-mediated diversification within the IgL locus of chicken DT40 cells is restricted to the transcribed IgL gene

Anjali R. Gopal, Sebastian D. Fugmann^*

^*Corresponding author for this work

National Institutes of Health

Research output: Contribution to journal › Journal Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	2062-2068
Number of pages	7
Journal	Molecular Immunology
Volume	45
Issue number	7
DOIs	https://doi.org/10.1016/j.molimm.2007.10.017
State	Published - 04 2008
Externally published	Yes

Keywords

DT40
Gene conversion
Immunoglobulin
Somatic hypermutation

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10.1016/j.molimm.2007.10.017

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title = "AID-mediated diversification within the IgL locus of chicken DT40 cells is restricted to the transcribed IgL gene",

abstract = "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.",

keywords = "DT40, Gene conversion, Immunoglobulin, Somatic hypermutation",

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AU - Gopal, Anjali R.

AU - Fugmann, Sebastian D.

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N2 - 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.

AB - 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.

KW - DT40

KW - Gene conversion

KW - Immunoglobulin

KW - Somatic hypermutation

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AID-mediated diversification within the IgL locus of chicken DT40 cells is restricted to the transcribed IgL gene

Abstract

Keywords

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