Abstract
AbstractB lymphocyte production in murine bone marrow is negatively regulated by sex steroids and the aim of this study was to identify early hormone sensitive checkpoints. Estrogen (E2) treatment reduced cμ+ pre-B cells, a change that occurred concomitantly with decreased Ig gene rearrangements and rag-1 transcripts. Estrogen decreased B lineage precursors in Ig transgenic mice, demonstrating that hormonal regulation is independent of the recombination process. B lineage precursors in Bcl-2 transgenic mice were resistant to estrogen treatment, suggesting that life/death decisions are involved in hormonal regulation. A previously uncharacterized population of CD43−cμ− B lineage precursors was identified in normal, Ig transgenic, and RAG−/− mice after estrogen treatment, revealing that down-regulation of CD43 can occur independent of Ig heavy chain expression. These cells expressed transcripts for both tdt andbcl-2, characteristics of early B-cell precursors. BrdU incorporation analysis revealed that the mitotic activity of early B-lineage cells is reduced in hormone-treated mice. We conclude that sex steroids modulate the production of B-lineage cells by influencing the differentiation, proliferation, and survival of early B-cell precursors. These findings are informative about mechanisms of hormonal regulation, as well as the significance of some differentiation-related events.
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