Failure of Lymphopoiesis after Adoptive Transfer of NF-κB–Deficient Fetal Liver Cells

Abstract

Mice deficient in the p65 subunit of NF-κB die during fetal development. Introduction of p50/p65-deficient fetal liver cells into lethally irradiated hosts resulted in a severe deficit of fetal liver–derived lymphocytes and their immediate precursors but an overabundance of fetal liver–derived granulocytes. Surprisingly, simultaneous transplantation of wild-type bone marrow cells rescued the production of p50/p65-deficient lymphocytes. Expression of immunoglobulin κ light chains on these rescued NF-κB–deficient B lymphocytes was normal. These results suggest that while p50 and p65 do not regulate the maturation of pre–B cells, NF-κB mediates the development or survival of an early lymphocyte precursor through regulation of an extracellular factor.