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• W2147784564 abstract "Variable (V) genes of immunoglobulins undergo somatic hypermutation by activation-induced deaminase (AID) to generate amino acid substitutions that encode antibodies with increased affinity for antigen. Hypermutation is restricted to germinal center B cells and cannot be recapitulated in ex vivo–activated splenic cells, even though the latter express high levels of AID. This suggests that there is a specific feature of antigen activation in germinal centers that recruits AID to V genes which is absent in mitogen-activated cultured cells. Using two Igh knock-in mouse models, we found that RNA polymerase II accumulates in V regions in B cells after both types of stimulation for an extended distance of 1.2 kb from the TATA box. The paused polymerases generate abundant single-strand DNA targets for AID. However, there is a distinct accumulation of the initiating form of polymerase, along with the transcription cofactor Spt5 and AID, in the V region from germinal center cells, which is totally absent in cultured cells. These data support a model where mutations are prevalent in germinal center cells, but not in ex vivo cells, because the initiating form of polymerase is retained, which affects Spt5 and AID recruitment." @default.
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• W2147784564 date "2014-10-06" @default.
• W2147784564 modified "2023-10-16" @default.
• W2147784564 title "Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo–activated cells" @default.
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• W2147784564 doi "https://doi.org/10.1084/jem.20131512" @default.
• W2147784564 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4203944" @default.
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