Divergent models of lymphoid lineage specification: do clonal assays provide all the answers?

Hematopoietic stem cells that drive blood development in mouse and man have been well characterized in recent years. In contrast, detailed analysis of the next stages of development, the progenitor cells that have begun to differentiate along specific hematopoietic lineages, is now only in its infancy. The process of myeloid differentiation has been relatively accessible to experimental manipulation due to the availability of culture systems able to support the progenitors for myeloid lineages, and the identification of cytokines capable of driving myeloid differentiation. Studies of early lymphoid differentiation, however, have lagged behind. In particular, the characterization of the first progenitors for the lymphoid lineages is far from complete, due mainly to inefficient assay systems for growing these cell lineages in vitro. Two laboratories have published conflicting data regarding the specification of lymphoid lineages in the mouse. Both groups of investigators utilize elegant clonal approaches to characterize progenitor cell subsets. While these experiments define lineage potential in the most rigorous manner possible, the divergent results suggest that clonal assays must be supplemented with more physiologic studies in order to define the actual differentiation pathways that function in vivo.