Developing Lymph Nodes Collect CD4+CD3− LTβ+ Cells That Can Differentiate to APC, NK Cells, and Follicular Cells but Not T or B Cells

AbstractFor a brief period during fetal lymph node organogenesis in mice, lymph node postcapillary high endothelial venules surprisingly express the Peyer's patch addressin MAdCAM-1. This expression allows initial seeding of this incipient structure by two unusual lymphocyte populations selectively expressing the Peyer's patch homing receptor integrin α4β7: CD4+CD3− oligolineage progenitors and TCR γδ+ T cells. We show here that CD4+CD3− cells are lineage-restricted progenitors that express surface lymphotoxin-β (LTβ) and the chemokine receptor BLR1 and that can become natural killer cells, dendritic antigen-presenting cells, and follicular cells of unknown outcome, but these cells do not become T or B lymphocytes. Since the necessity of lymphotoxin in lymphoid organ development has been shown, we propose that the novel subset of CD4+ CD3−LTβ+ fetal cells is instrumental in the development of lymphoid tissue architecture