TCRbeta enhancer activation in early and late lymphoid progenitors

An earlier report from our laboratory indicates that the activation of the T cell receptor (TCR) beta enhancer (Ebeta) is not always an indicator of T lineage potential in bone marrow-resident pre-lymphocytes. In order to more precisely investigate the consequences of Ebeta activation in lymphopoiesis, a genetic reporter animal, in which the expression of green fluorescent protein (GFP) is controlled by Ebeta, was used to examine two well-defined lymphopotent populations. Adoptive transfer experiments suggest that primitive lymphoid precursor populations (specifically, hematopoietic stem cells) consist of two discrete-populations discernible by Ebeta-GFP activation, although the two populations display no overt differences in lineage potential. In contrast, subsets of more differentiated pre-lymphocytes (specifically, common lymphoid progenitors), while also discernible by Ebeta-GFP activation, display different capacities for reconstituting lymphoid compartments. Interestingly, late lymphoid progenitors containing inactive Ebeta elements generated both T and B cells in vivo, in accord with the original description of this population; however, progenitors containing active Ebeta elements displayed an unexpected bias toward the B lineage. Our findings suggest that Ebeta activation is an indicator of B lineage specification in late, but not early lymphoid precursors.