This review describes an improved characterization of early B-lymphocyte pr
ecursors in mice and the remarkable sensitivity of the same cells to hormon
es. The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) was used
as a marker to image and characterize bone marrow cells lacking all lineag
e-associated markers. Most early TdT(+) precursors have a distinctive densi
ty of c-kit and express the interleukin-7R alpha chain, as well as flt-3/fl
k2, but lack CD34. An understanding of those cell surface properties made i
t possible to obtain highly enriched, viable cells with the potential to gi
ve rise to CD19(+) lymphocytes in culture. A series of other flow cytometry
and culture experiments suggested a possible differentiation sequence for
these early pro-B cells. This new model was used to advantage in our studie
s of sex steroids, it appears that early precursors represent a hormone-sen
sitive control point fur determining numbers of new B lymphocytes that are
produced within bone marrow. We also compare and contrast these findings wi
th B lymphopoiesis in humans.