Abstract
Cytokine signaling through the tyrosine kinase receptor flt3 and the hematopoietin Interleukin-7-receptor a chain (IL7Ra) is critically involved in regulation of B lymphopoiesis. Specifically, we have recently demonstrated that mice double deficient in flt3 and IL7Ra signaling fail to support B cell commitment and development during embryogenesis as well as in adult hematopietic tissues (
Sitnicka et al, J. Exp. Med; 198:1495, 2003
). Previous studies have through generation of IL7Ra knockout mouse on a Bcl-2 transgenic background suggested that IL-7 induced triggering of anti-apoptotic pathways is critically involved in T cell but not B cell development (Akashi et al, Cell; 89:1033, 1997
, Kondo et al, Immunity; 7:155, 1997
). Thus, we here investigated whether anti-apoptotic signaling might rather be involved in flt3-dependent B cell development, through generation of a H2k driven human Bcl-2 transgenic/Flt3 ligand (FL)−/− (Bcl-2/FL−/−) mice. Strikingly, numbers of Common Lymphoid Progenitors (CLP; lin−c-kitloSca-1loIL7Ra+), pro-B (B220+CD19+AA4.1+CD43+), pre-B (B220+CD43−IgM−) and mature B cells (B220+CD43−IgM+) in the BM of 7–8 weeks old Bcl-2/FL−/− mice were all comparable to those observed in wild type mice. More importantly, the pronounced reductions in CLP, pro-B and pre-B progenitors seen in FL−/− mice on a wild type background were compensated by approximately 50% when FL-deficiency was rather induced on a bcl-2 transgenic background (Bcl-2/FL−/−). Thus, in contrast to IL7Ra, the critical role of flt3 in B cell commitment and development might involve triggering of anti-apoptotic pathways.Author notes
Corresponding author
2005, The American Society of Hematology
2004
