Abstract:
:Antibody specificity and diversity is generated in B cells during germinal center maturation through clonal expansion while they undergo class-switch recombination and somatic hypermutation. Here we demonstrate that the transcriptional repressor Bcl-6 mediates this phenotype by directly repressing ATR in centroblasts and lymphoma cells. ATR is critical in replication and DNA damage-sensing checkpoints. Bcl-6 allowed B cells to evade ATR-mediated checkpoints and attenuated the response of the B cells to exogenous DNA damage. Repression of ATR was necessary and sufficient for those Bcl-6 activities. CD40 signaling 'rescued' B cells from those effects by disrupting the Bcl-6 transcription-repression complex on the promoter of the gene encoding ATR. Our data demonstrate a transcriptional regulatory loop whereby Bcl-6 mediates the centroblast phenotype through transient silencing of ATR.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Ranuncolo SM,Polo JM,Dierov J,Singer M,Kuo T,Greally J,Green R,Carroll M,Melnick Adoi
10.1038/ni1478subject
Has Abstractpub_date
2007-07-01 00:00:00pages
705-14issue
7eissn
1529-2908issn
1529-2916pii
ni1478journal_volume
8pub_type
杂志文章abstract::T cell homeostasis is crucial for a functional immune system, as the accumulation of T cells resulting from lack of regulatory T cells or an inability to shut down immune responses can lead to inflammation and autoimmune pathology. Here we show that Blimp-1, a transcriptional repressor that is a 'master regulator' of ...
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pub_type: 杂志文章
doi:10.1038/ni1053
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