The production of B cells is a complex process determined by well-timed combinations of intrinsic factors and environmental cues that guide the differentiation of primitive progenitors in the bone marrow. Expression of several key transcription factors and receptor-stromal cell ligand interactions are landmarks of the earliest events in B lymphopoiesis in adult bone marrow. We describe this as a gradual loss of options for other blood cell lineages coincident with gain of essential properties. Experimental, stress or infection-related deregulation may change B cell fate specification, commitment or population dynamics, and consequently the production rate of mature populations. © 2005 Elsevier Ltd. All rights reserved.