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We have studied both in vitro and in vivo the formation of lymphocyte progenitors before blood circulation (day 9 of gestation) has started in the mouse embryo, and we have determined the tissue where this occurs. The results demonstrate that the yolk sac of embryos at day 8 and day 8.5 of gestation contains precursor cells that can give rise, in vivo and in vitro, to mature T and B lymphocytes. No lymphoid precursors were found in the embryo proper at this stage of mouse development. The yolk sac cells with lymphocyte precursor potential are most likely multipotent stem cells rather than cell-lineage-determined T- and/or B-lymphocyte progenitors. The defined in vitro assays described here that support differentiation of yolk sac stem cells along the T- or B-lymphocyte pathways also may now facilitate the study of the molecular events leading to cell-lineage commitment of lymphocyte progenitors in the mouse embryo.

At day 8-8.5 of mouse development the yolk sac, not the embryo proper, has lymphoid precursor potential in vivo and in vitro.