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Ana Marie Landin,Daniela Frasca,Martina Scallan,Patrick Harrison,James Hagman, and Bonnie Blomberg
The Journal of Immunology
The role of Pax5 and E47 on AID expression in B lymphocytes of Aged BALB/c Mice
In Press
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Previous results from our laboratory demonstrated that stimulated enriched (95%) B cells from senescent mice (19 to 24 months) have an intrinsic defect in class switch recombination (CSR), and a decrease seen in both Pax5 and E47. The decrease in both Pax5 and E47 is proportional to the decrease in activation induced cytidine deaminase (AID) with aging. Binding sites for both Pax5 and E47 have been identified in the gene for AID, Aicda, and stimulation of B cells results in the recruitment of Pax5 and E47 to the Aicda gene and its expression. Our current results show that overexpression of both E47 and Pax5 rescues levels of AID and CSR in old B lymphocytes to young-like levels. Furthermore, exogenous retroviral E47 mRNA is more stable than the endogenous E47 due to the removal of the 3’UTR. Overexpression of Pax5 leads to up-regulation of E47 in both primary B cells and 293T cells; however, overexpression of E47 up-regulates Pax5 in B cells but not in 293T cells. Nuclear extracts from B cells of senescent mice show lower levels of binding consistent with reduced levels of E47 and Pax5 in aging. Using a DsRed lentiviral vector driven by the Aicda promoter and containing the E47 and Pax5 enhancer region, we show that in 293T cells DsRed is only expressed when the cells are co-transduced with E47 and/or Pax5.
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