The first 3 days of B-cell development in the mouse embryo.

B-lineage-committed cells are believed to arise in the liver of mouse embryos at 14 days after coitus (dpc). However, pre-B-specific gene transcripts and DJH gene rearrangements have been detected in earlier, midgestation embryos. We describe here a population of c-kit(+)AA4.1(+)CD19(+)Pax5(+) cells present in the aorta-gonad-mesonephros (AGM) area and in the livers of 11-dpc mouse embryos. In contrast to multipotent c-kit(+)AA4.1(+)CD19(-) hematopoietic stem cells (HSCs), these c-kit(+)AA4.1(+)CD19(+) progenitors differentiated only to B-lineage cells in vitro. We propose that mouse embryonic B lymphopoiesis starts earlier than previously thought, at 10 to 11 dpc, both in liver and extra-liver hematopoietic sites. The B-cell differentiation program is not delayed with respect to the emerging lymphohematopoiesis events in the midgestation mouse embryo (8-9 dpc).