Transcriptional regulation in early B cell development

Abstract

Transcription factors and signalling molecules are important for both lineage commitment and lineage-specific regulation. The B cell specification factor Pax5 plays a dual role in B lineage commitment. Simultaneously, it potentiates and limits lineage choice by activating genes that are required for the B cell program while repressing lineage-inappropriate genes; more than 100 of the latter have now been identified. In this context, repression of the tyrosine kinase Flt3 has been shown to be essential for B lineage commitment. Regulation of antigen receptor recombination constitutes another level at which lineage specificity is determined, and the identification of two factors, E47 and FOXP1, which regulate the activity of the recombinase enzymes in B lineage cells, provides insight into the mechanisms that determine this. New information regarding the control of ordered recombination and allelic exclusion comes from studies of cis-acting elements within the Ig loci.