What disrupts healthy immune system formation?
Pax5 (paired box) is a protein encoded by the Pax5 gene, which belongs to the family of Pax transcription factors. These control when transcription — one of the steps on the path to gene expression — occurs, and how much genetic information is passed on. B cells, a vital component of the adaptive immune system, are lymphocytes (white blood cells) working to make antibodies against antigens by acting as antigen-presenting cells (APCs). Research has shown that Pax5 is in command of the intricate regulatory network involved in B cell signalling, adhesion, migration and immune function. The 'Characterization of the b-cell-specific gene regulatory network by genome-wide identification of direct pax5 target genes' (Pax5targets) project aimed to analyse all direct Pax5 target genes during the development of B cells. A specific mouse strain was generated for identification of Pax5-binding sites across the entire genome. This was done using chromatin modification, which has been proved effective in identifying active and repressed promoters and certain regulatory elements. The EU-funded project quantified gene expression in B cell progenitors (pro-B) as well as in mature B cells. Resulting data allowed researchers to work towards defining all the changes in gene expression that take place during the development of B cells. Further studies also set the stage for which genes need Pax5 for their correct expression during B cell development. Genome-wide Pax5 binding sites were identified, as were other active elements and promoters. Analyses of such data revealed that Pax5 has numerous direct targets both in pro-B and mature B cells. This verifies its role in the maintenance of B cell identity. Project partners also discovered that Pax5 affects the expression of numerous genes whose loci are not directly bound by the transcription factor. The outcomes of the Pax5targets project have set the stage for further investigation of important regulators of B cell development as well as of the function of these novel transcription factors. Building on this work, researchers will better understand and describe the molecular mechanisms underlying B cell development.
