Abstract
B cell development is influenced by interactions between B cell progenitors and stromal cells. The precise mechanisms by which these interactions regulate B cell differentiation are currently unknown. Flt3 ligand (FL) is a growth factor which stimulates the proliferation of stem cells and early progenitors. Mice deficient for the FLT3 receptor exhibit severe reductions in early B lymphoid progenitors. We have previously described a clonal assay in vitro which allows us to follow the entire B cell differentiation pathway from uncommitted progenitors to mature, immunoglobulinβsecreting plasma cells. The growth factor combination of interleukin (IL)β11, mast cell growth factor (MGF) and ILβ7 was shown to maintain the differentiation of these hematopoietic precursors into B cell progenitors capable of giving rise to functionally mature B cells in secondary cultures. Here, we show that FL in combination with ILβ11 and ILβ7 is sufficient to support the differentiation of uncommitted progenitors from day 10 yolk sac (AA4.1^+^) or day 12 fetal liver (AA4.1^+^ B220^β^ Macβ1^β^ Scaβ1^+^) into the B lineage. The frequency of B cell progenitors obtained in these conditions was similar, if not better, than the frequency of B cell precursors that arose when cultured in ILβ11+MGF+ILβ7. Furthermore, the growth factor combination of ILβ11+FL+ILβ7 was able to maintain the potential of bipotent precursors giving rise to both the B and myeloid lineages in secondary cultures. We also show that FL synergizes with ILβ7 in the proliferation of committed B220^+^ proβB cells and may contribute to the maintenance of an earlier proβB cell population. Together, these results show that FL is important in supporting the differentiation and proliferation of early B cell progenitors in vitro.