ESTROGEN SUPPRESSES STROMAL CELL-DEPENDENT LYMPHOPOIESIS IN CULTURE

Numbers of pre-B cells change dramatically and reciprocally in respons e to estrogen levels in mice, suggesting that normal lymphopoiesis may be under hormonal control. However, little is known of the mechanisms involved in this process. We found that estrogen receptor mRNA was de tectable by RT-PCR in lymphocyte supporting stromal cells as well as B lymphocyte precursors. Unlike glucocorticoids, estrogen did not induc e apoptosis in isolated B lineage lymphocytes or interfere with their responsiveness to IL-7 in semisolid agar, Estrogen did inhibit clonal expansion of B cell precursors in a limiting dilution-type assay when the lymphocytes were cultured on a stromal fell clone. In other experi ments, B cell precursors at particular stages of differentiation were isolated by cell sorting and cocultured with stromal cells for 4 days, This revealed that some subsets were more sensitive to an estrogen-co ntaining environment than others. Although numbers of recovered cells were greatly reduced, the remaining lymphocytes had undergone relative ly normal differentiation, The surviving population was enriched in ce lls that had acquired cytoplasmic mu chains, BP-1 Ag, and clonability with IL-7, Hormone-mediated inhibition occurred in serum and phenol-re d free medium, and in cultures replete with IL-7. Direct contact betwe en stromal cells and lymphocytes was not required, Furthermore, suppre ssion resulted when stromal cells alone were treated with the hormone, These findings indicate that estrogen may regulate B lymphopoiesis vi a its influence on the microenvironment and that estrogen-induced stro mal cell genes merit further study.