¹Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

Correspondence: Dr SL Nutt, Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. E-mail: nutt@wehi.edu.au

²These authors contributed equally to this work.

³Current address: Department of haematology, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 OXY, UK.

Received 11 October 2007; Accepted 13 October 2007; Published online 13 November 2007.

Abstract

The activity of the transcription factor paired box gene 5 (Pax5) is essential for many aspects of B lymphopoiesis including the initial commitment to the lineage, immunoglobulin rearrangement, pre-B cell receptor signalling and maintaining cell identity in mature B cells. Deregulated or reduced Pax5 activity has also been implicated in B-cell malignancies both in human disease and mouse models. Candidate gene approaches and biochemical analysis have revealed that Pax5 regulates B lymphopoiesis by concurrently activating B cell-specific gene expression as well as repressing the expression of genes, many of which are associated with non-B cell lineages. These studies have been recently complemented with more exhaustive microarray studies, which have identified and validated a large panel of Pax5 target genes. These target genes reveal a gene regulatory network, with Pax5 at its centre that controls the B-cell gene expression programme.