TGFβ can inhibit the in vitro proliferation, survival, and differentiation of B cell progenitors, mature B lymphocytes, and plasma cells. Unexpectedly, TGFβ1−/− mice were found to have age-dependent reductions in the bone marrow (BM) B cell progenitor and immature B cell compartments. Normal (C57BL/6) BM B lineage cell responses to TGFβ1 in IL7 cultures showed differential outcomes of B cell progenitor subsets. Low doses of TGFβ1 (1.6 pM) reduced the pro-B-enriched population at every timepoint of a week-long culture. In contrast, pre-B cells were initially reduced in number and subsequently increased compared to IL7 alone. Thus, pM TGFβ treatment of IL7-stimulated BM B lineage cells results in a significant 4-fold increase (p= 0.0015) in the pre-B cell growth rate. Cultures of sorted normal BM indicate that pro-B cells, and the earliest pre-B cells that do not express the BPI marker, are also sensitive to these inhibitory effects. The reductions in pro-B cells, as recapitulated with CD 19+ Rag1−/− BM, were associated with an accumulation of subdiploid cells at 16 hours, and an accumulation of diploid (resting) cells by 72 hours in TGFβ1. Pro-B cell recoveries from Bcl2-transgenic BM cultures were also reduced in response to TGFβ1. This suggests that although TGFβ1 can induce pro-B cell death early on, cell cycle arrest may be the predominant mechanism responsible for reduced pro-B cell recoveries in our cultures. Pre-B cells derived from large BP1+ sIgM− BCP cultures are initially reduced, but are increased in number at 5 and 7 days. This indicates that the large pre-B cell stage is responsible for the positive read-out in earlier experiments. Collectively, these results indicate that TGFβ1 is required for normal B cell development in vivo, and that subsets of BCP are differentially affected by this cytokine according to their stage of differentiation.