Transcriptional regulation of early B-lymphocyte differentiation

Differentiation of hematopoietic progenitors into the B-lymphocytc lineage requires co-ordination of a complex network of transcriptional regulators. Lineage specificity is likely to result From combinatorial mechanisms of ge ne regulation. Four general functions are mediated by transcription factors in the differentiating pro-B cell. First, a cascade of B-cell-restricted t ranscription Factors is upregulated. Second, genes involved in the specific ation of other cell fates are repressed. Both activation and repression req uire the participation of different classes of transcriptional regulators, including proteins of the Ikaros family that can recruit chromatin-modifyin g complexes. Third, the expression of genes that facilitate B-cell prolifer ation and differentiation are activated, Lastly, genes required for recombi nation are expressed and targeted to the immunoglobulin loci, thus initiati ng the characteristic rearrangement of thr immunoglobulin genes. The intera ctions and functions of transcription factors in pro-B-cell differentiation are discussed.