Differential Programming of B Cells in AID Deficient Mice

The Aicda locus encodes the activation induced cytidine deaminase (AID) and is highly expressed in germinal center (GC) B cells to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes. Besides these Ig specific activities in B cells, AID has been imp...

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Published in:PloS one Vol. 8; no. 7; p. e69815
Main Authors: Hogenbirk, Marc A., Heideman, Marinus R., Velds, Arno, van den Berk, Paul CM, Kerkhoven, Ron M., van Steensel, Bas, Jacobs, Heinz
Format: Journal Article
Language:English
Published: United States Public Library of Science 29.07.2013
Public Library of Science (PLoS)
Subjects:
Animals
Antigens
B-Lymphocytes - enzymology
B-Lymphocytes - metabolism
Biology
Cancer
Cell activation
Cell cycle
Class switching
Correlation analysis
Cytidine deaminase
Cytidine Deaminase - deficiency
Cytidine Deaminase - genetics
Demethylation
Dendritic cells
Deoxyribonucleic acid
DNA
DNA methylation
DNA Methylation - genetics
Epigenetics
Gene expression
Genomes
Genotype
Immunoglobulins
Loci
Lymphocytes B
Lymphoma
Mice
Mice, Mutant Strains
Mutation
Recombination
Ribonucleic acid
RNA
Single-nucleotide polymorphism
Somatic hypermutation
Stem cells
Stress response
Studies
Transcription
Netherlands
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:The Aicda locus encodes the activation induced cytidine deaminase (AID) and is highly expressed in germinal center (GC) B cells to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes. Besides these Ig specific activities in B cells, AID has been implicated in active DNA demethylation in non-B cell systems. We here determined a potential role of AID as an epigenetic eraser and transcriptional regulator in B cells. RNA-Seq on different B cell subsets revealed that Aicda(-/-) B cells are developmentally affected. However as shown by RNA-Seq, MethylCap-Seq, and SNP analysis these transcriptome alterations may not relate to AID, but alternatively to a CBA mouse strain derived region around the targeted Aicda locus. These unexpected confounding parameters provide alternative, AID-independent interpretations on genotype-phenotype correlations previously reported in numerous studies on AID using the Aicda(-/-) mouse strain.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: MAH BvS HJ. Performed the experiments: MAH MRH PCMvdB. Analyzed the data: MAH AV HJ. Contributed reagents/materials/analysis tools: RMK. Wrote the paper: MAH HJ.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0069815