Age-related differences in the E2A-encoded transcription factor E47 in bone marrow-derived B cell precursors and in splenic B cells.

We have investigated the effects of aging on the E2A-encoded transcription factor E47, a key regulator of B cell functions, in B cell precursors and in splenic B cells. Here, we show that old mice can be classified as severely depleted, moderately depleted or not depleted mice, according to the percentage of pre-B cells in their bone marrow. IL-7-expanded populations of pro-B/early pre-B cells from bone marrow of both severely depleted and moderately depleted old mice exhibit a reduced E47 DNA-binding and expression compared to young mice, and this defect in severely depleted old mice is more dramatic than that in moderately depleted old mice. However, mRNA levels were comparable, suggesting that E47 in the bone marrow is not transcriptionally regulated. In the spleen, activated B cells from both severely depleted and moderately depleted old mice show a lower E47 DNA-binding and expression than young mice. However, in contrast to precursor B cells, E47 DNA-binding and expression are similarly and only moderately reduced in both severely depleted and in moderately depleted mice. The mRNA levels were found to be decreased in stimulated splenic B cells from old as compared to young mice, suggesting that E47 mRNA in the spleen may be both transcriptionally and/or post-transcriptionally regulated.