Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells

PloS One
Alan M WilliamsDavid G Schatz

Abstract

The activation induced cytosine deaminase (AID) mediates diversification of B cell immunoglobulin genes by the three distinct yet related processes of somatic hypermutation (SHM), class switch recombination (CSR), and gene conversion (GCV). SHM occurs in germinal center B cells, and the transcription factor Bcl6 is a key regulator of the germinal center B cell gene expression program, including expression of AID. To test the hypothesis that Bcl6 function is important for the process of SHM, we compared WT chicken DT40 B cells, which constitutively perform SHM/GCV, to their Bcl6-deficient counterparts. We found that Bcl6-deficient DT40 cells were unable to perform SHM and GCV despite enforced high level expression of AID and substantial levels of AID in the nucleus of the cells. To gain mechanistic insight into the GCV/SHM dependency on Bcl6, transcriptional features of a highly expressed SHM target gene were analyzed in Bcl6-sufficient and -deficient DT40 cells. No defect was observed in the accumulation of single stranded DNA in the target gene as a result of Bcl6 deficiency. In contrast, association of Spt5, an RNA polymerase II (Pol II) and AID binding factor, was strongly reduced at the target gene body relative to the tran...Continue Reading

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Citations

Mar 17, 2017·European Journal of Immunology·Paulina M BudzyńskaJukka Alinikula
Feb 13, 2018·Scandinavian Journal of Immunology·P M BudzyńskaJ Alinikula
Jun 27, 2019·Poultry Science·Nikhil K NuthalapatiGregory T Pharr
Dec 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alina TarsalainenJukka Alinikula

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Methods Mentioned

BETA
deamination
flow cytometry
PCR
ChIP-seq
ChIP
transfection

Software Mentioned

MACS
Sequencher
_ toolkit
Flow Jo
bowtie
fastx

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