Of all mature hematopoietic cell types, lymphocytes are most sophisticated in terms of their combination of highly regulated, differentiated characteristics with virtually unlimited proliferative potential and the ability to respond correctly in a wide variety of microenvironments. The developmental process that generates these cells from pluripotent hematopoietic precursors needs to install regulatory circuits so robust that they can faithfully maintain cell-type-specific characteristics in different places, different times, and after different numbers of divisions. Exciting recent advances are now helping us begin to understand the regulatory cascade that pushes cells through the transition from pluripotent progenitor to committed B or T lymphocyte.
New data from both molecular and cellular investigations have revolutionized our understanding of the molecular alterations inside developing hematopoietic cells that trigger differentiation into lymphocytes. A picture has emerged of a network of interactions among transcription factors that systematically activates successive stages of differentiation in the B-cell lineage. This is complemented by experiments that have identified a series of progressive changes in developmental plasticity in cells approaching commitment to the T lineage. Knockout and retroviral transfer technologies have made it possible to address the precise roles of particular regulatory genes in these processes. The effects of some genes with similar actions in the T and B lineages, and the effects of others that are opposite in their effects on the two lineages, have reignited debate on the lineage relationships between these two classes of lymphocytes. The rules for interaction among different transcription factors and the identities of key lineage-determining target genes are becoming discernible
5th Gene Regulation
Parallels and contrasts between the results emerging for T and B cell development would certainly accelerate progress in both areas. But as a rule, researchers working on these two related cell types have little opportunity to interact at immunology meetings, because these cell types are viewed as exemplifying different branches of immune response. This segregation has little rationale in dealing with the earliest stages of B and T lymphocyte development from common precursors, where only the comparison between mechanisms involved in initiating these two pathways can shed light on the basis of developmental choice. A crucial aspect of the conference we propose to organize is the direct juxtaposition of researchers addressing parallel or divergent molecular mechanisms in early stages of B and T cell development.
This conference is explicitly planned to bring together researchers working on the transcriptional mechanisms regulating gene expression in lymphocyte development with those addressing the impact of regulatory changes on developmental choices. The goal is to provide a lively, critical audience for models proposing specific causal linkages between transcription factors, their target genes, and a resulting change in developmental fate.