Peer-Reviewed Journal Details
Mandatory Fields
Ana Marie Landin,Daniela Frasca,Patrick Harrison,Martina Scallan,James Hagman, and Bonnie Blomberg
2010
Unknown
Journal of Immunology
Pax5 and E47 regulate AID and class switch recombination in young and aged BALB/c mice
In Press
()
Optional Fields
184
Our laboratory has shown that stimulated B cells from senescent mice (19 to 24 months) have an intrinsic defect in class switch recombination (CSR) that is coincident with reduced E47. In aging, the decrease in E47 correlates proportionally with levels of activation induced cytidine deaminase (Aicda/AID) transcripts; but, other transcription factors may be involved. Pax5 has been shown to play a role in CSR. The purpose of the present study was to determine whether 1) Pax5 is decreased with age, 2) the decrease in Pax5 correlates with decreased CSR in aged B cells, 3) increased E47 and/or Pax5 can rescue the decreased CSR observed in these cells and 4) depletion of Pax5 down-regulates E47 and/or AID expression. Here, we demonstrate that E47 and Pax5 are both down-regulated in mature splenic B cells of aged mice. Endogenous E47, Pax5 and IgG1 are increased in old as well as young primary stimulated B cells in response to exogenously expressed E47. We successfully rescued levels of both E47 and Pax5 mRNA and protein in transduced splenic B cells of aged mice when compared to young untransduced controls. Restoration of Pax5 expression increased E47, AID and CSR in B cells from aged mice. Conversely, silencing Pax5 by means of siRNA transfection decreased E47 and AID expression significantly. These results suggest a possible feedback mechanism between E47 and Pax5. Our results show that E47 and Pax5 cooperate to regulate AID and CSR in both young and old B lymphocytes.
Grant Details