Fetal lymphocyte progenitors efficiently generate innate-like B cells but make a more limited contribution to the production of conventional lymphocytes.

Various progenitor populations with lymphoid potential emerge in multiple waves of fetal development and can do so independent from hematopoietic stem cells (HSCs). This review compares and contrasts data from our analysis of a mutant mouse in which fetal but not adult lymphopoiesis is intact with results from lineage tracing studies. This allowed us to address how efficiently and how long fetal lymphoid progenitors generated lymphoid progeny after birth. We then present, based on the data in these reports, a working model proposing that fetal lymphocyte progenitors efficiently generate innate-like B-1 and marginal zone B cells, but their contribution to the production of B and T cells of the adaptive immune system is more limited. Instead, lymphocyte development from adult HSCs is necessary to fill secondary lymphoid tissues with conventional lymphocytes, and fetal progenitors lack the potential to do so. We propose that, in addition to generating innate-like effectors, the key role of fetal lymphoid progenitors is to produce a sufficient number of B and T cell progeny, particularly in the intestines, so that the newborn and neonate have functional immunity until lymphopoiesis from HSCs is fully established.