B-cell development and proposed model of action for HK-1. (A) The drawing shows a simplified model of bone marrow B lymphocyte development. B-cell development occurs through several stages in a complex bone marrow microenvironment. ELP indicates early lymphoid progenitor; and CLP, common lymphoid progenitor. (B) The lack of HK-1 in TAC4^−/− bone marrow cultures resulted in a specific increase of pro-B cells compared with WT cultures. The addition of HK-1 to these cultures had no effect on the elevated number of pro-B cells, suggesting that an earlier developmental event may be responsible for this phenotype. (C) Cultures derived from purified TAC4^−/− hematopoietic stem cells also resulted in an increase of pro-B cells compared with WT control cultures. In contrast to total bone marrow cultures, daily addition of HK-1 to LTRC- and ITRC-derived cultures resulted in significantly decreased numbers of pro-B cells in WT- and HK-1-deficient cultures, suggesting that HK-1 plays an inhibitory role during hematopoiesis.