B lymphocyte precursors in embryonic and adult W anemic mice

Mice homozygous for mutations at the dominant spotting or W locus on chromosome 5 have been extensively used as models of severe macrocytic anemia caused by defective hemopoietic stem cells. We examined cells of the developing B lineage in adult and embryonic W anemic mice both by phenotypic analyses and by three distinctly different functional assays for B lymphocyte precursors. Adult W/Wv mice had normal numbers of B cells in the spleen and bone marrow, and normal numbers of pre-B cells and cells identified by a monoclonal antibody directed to a B lineage cell surface antigen (14.8) in the bone marrow. Embryonic W/Wv and Wx/Wx mice had hypoplastic liver development at 16 days gestation with a corresponding reduction in absolute numbers of pre-B cells, 14.8+ cells, and clonable granulocyte-macrophage progenitor cells, although their frequencies were normal. As expected, spleen colony-forming units were greatly reduced both in absolute number and frequency. Adult bone marrow cells and fetal liver cells from W anemic mutants generated B cells in vitro as well as did cells from normal littermates, but W anemic cells failed to generate B lymphocytes as well in vivo. These observations likely reflect differences in precursor cells that contribute to B cell formation in these assays, and suggest that early B lineage precursors are reduced or defective in W anemic mice.