Increased fetal and extramedullary hematopoiesis in Fas-deficient C57BL/6-lpr/lpr mice

In this study, we examined the consequences of Fas deficiency on hematopoie sis in C57BL/6-lpr/lpr mice. We found a striking extramedullary increase in hematopoietic progenitor cells, comprising erythroid and nonerythroid line ages alike. These modifications preceded the lymphadenopathy, because early progenitors (colony-forming units-spleen [CFUS] day 8) were already augmen ted in day-id fetal livers of the lpr phenotype. Three weeks after birth, C FU-S increased in peripheral blood and spleen and colony-forming cells (CFU -C) began to accumulate 1 to 3 weeks later. Extramedullary myelopoiesis aug mented progressively in Fas-deficient mice, reaching a maximum within 6 mon ths. By then, mature and immature myeloid cells had infiltrated the spleen, the liver, and the peritoneal cavity, Similar changes occurred in C57BL/6- gld/gld mice, indicating that they resulted from Fas/FasL interactions. Med ullary hematopoiesis was not significantly modified in adult mice of either strain. Yet, the incidence of CFU-S decreased after pas cross-linking on n ormal bone marrow cells in the presence of interferon gamma, consistent wit h a regulatory function of Fas/FasL interactions in early progenitor cell d evelopment. These data provide evidence that Fas deficiency can affect hema topoiesis both during adult and fetal life and that these modifications occ ur independently from other pathologies associated with the lpr phenotype. (C) 1999 by The American Society of Hematology.