Estrogen influences the differentiation, proliferation, and survival of early B-lineage precursors.
B 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 cmu(+) 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(-)cmu(-) 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 and bcl-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. (Blood. 2000;95:2059-2067)
Medina
K L
KL
Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Strasser
A
A
Kincade
P W
PW
D000818:Animals; D015703:Antigens, CD; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology*; D001853:Bone Marrow / Q000276:immunology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D004967:Estrogens / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051917:Leukosialin; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism
D015703:Antigens, CD; D018941:Antigens, CD19; D004967:Estrogens; D018398:Homeodomain Proteins; D051917:Leukosialin; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens; D001973:Bromodeoxyuridine