Fetal Lymphoid Progenitors Become Restricted to B-1 Fates Coincident with IL-7Rα Expression.

Abstract

B-1 cells represent a sub-fraction of B lymphocytes that participate in T cell-independent antibody production and contribute to innate immunity. While the production of B-1 cells is favored during the fetal waves of lymphopoiesis, it has been unclear when and how that differentiation option is specified. To clarify this, lymphoid and hematopoietic progenitors of fetal liver (FL) and adult bone marrow (ABM) were examined for the B cell differentiation potential. Mouse common lymphoid progenitors (CLPs) and more primitive KSL fraction of FL and ABM were transferred to SCID mice and donor-derived B cell subsets were analyzed 4 weeks later. CLPs were also cultured on ST2 stromal cells for 6 days prior to transplantation. While Lin- IL-7Rα+ CLPs from ABM differentiated to B-1, B-2 and marginal zone B (MZB) cells, equivalent cells from d15 FL differentiated mostly to B-1a cells. We found that fetal CLPs had less ability to colonize the bone marrow than adult CLPs. However, the fetal/adult difference was already present when progenitors were cultured in an identical condition before transplantation. More primitive KSL fraction of FL could generate the same broad spectrum of B cells typical of adults, including splenic MZB cells. In conclusion, we argue that FL and ABM-CLPs are intrinsically different regarding B-1/B-2 fates and the difference is acquired just before or coincident with the acquisition of IL-7Rα expression.