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 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.
Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Marc A
MA
Hogenbirk
Marinus R
MR
Heideman
Arno
A
Velds
Paul C M
PC
van den Berk
Ron M
RM
Kerkhoven
Bas
B
van Steensel
Heinz
H
Jacobs
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000172:deficiency* / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005838:Genotype; D051379:Mice; D008817:Mice, Mutant Strains; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase