The age-related decrease in E47 DNA-binding does not depend on increased Id inhibitory proteins in bone marrow-derived B cell precursors.

Abstract

Our previous results showed that decreased numbers of pre-B cells in aged mice were associated with decreases in surrogate light chain, lambda5, and transcription factors E47/E12. In the present paper, we have analyzed IL-7-expanded populations of pro-B/early pre-B cells to evaluate whether the age-related reduction in E47 DNA-binding could be attributed to reduced E47 expression and/or increased Id expression. According to the percentage of pre-B cells present in their bone marrow, old mice were classified as severely depleted (>80% loss in pre-B cells, 50% loss in pro-B cells), or moderately depleted (20-80% loss in pre-B cells). Results herein show that IL-7-stimulated pro-B/pre-B cells from both severely depleted and moderately depleted old mice exhibit a reduced E47 DNA-binding capacity compared to young mice, and this defect in severely depleted old mice is more dramatic than that in moderately depleted old mice. Id proteins, which are inhibitors of E47, are not increased in nuclear extracts of IL-7-expanded pro-B/early pre-B cells from severely depleted or moderately depleted old mice. We therefore conclude that the reduced expression of E47 protein alone in severely depleted and to a lesser extent in moderately depleted old mice explains the reduced amount of E47-DNA binding.