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- W4313373119 abstract "Abstract Cell division is essential for B cell differentiation to a plasma cell (PC). While the cell division coupled changes in the expression of transcription factors that coordinate the PC program have been described, little is known regarding how these factors coordinate the proliferative program. To address this, we exploited an adoptive transfer system and monitored the cell division/differentiation kinetics in response to lipopolysaccharide (LPS). In this system, wildtype (WT) B cells undergo at least 8 cell divisions before differentiating into PC, and the same requirement is also observed following NP-ficoll or influenza immune challenge. Modeling division rates over time identified a proliferative burst between 48 and 60 hours following LPS injection. In contrast, Interferon Regulatory Factor 4-deficient (IRF4−/−) B cells divided but failed to undergo the proliferative burst, stalling at divisions 2–6. To assess the scope of IRF4-dependent reprogramming, WT and IRF4−/− B cells at divisions 0, 1, and 3–6 were sorted for ATAC- and RNA-seq. RNA-seq data revealed hundreds of differentially expressed genes (DEGs) when IRF4 was deleted, a subset of which included MYC target genes. Indeed, IRF4−/− cells failed to upregulate MYC compared to WT cells and consequently, we observed little increase in cell size following immune challenge. Furthermore, IRF4−/− B cells exhibited aberrant cell cycle distribution when compared to WT cells at the same timepoint and division. ATAC-seq data also exposed hundreds of differentially accessible regions, the majority of which contained a known IRF4 binding motif and mapped to a corresponding DEG. Together, these data reveal a critical role for IRF4 in maintaining the proliferative response." @default.
- W4313373119 created "2023-01-06" @default.
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- W4313373119 date "2020-05-01" @default.
- W4313373119 modified "2023-09-27" @default.
- W4313373119 title "IRF4 regulates the proliferative capacity of activated B cells during B cell differentiation" @default.
- W4313373119 doi "https://doi.org/10.4049/jimmunol.204.supp.151.26" @default.
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