Pax5 maintains cellular identity by repressing gene expression throughout B cell differentiation.
The transcription factor Pax5 is required for many aspects of B-lymphopoiesis including lineage commitment, immunoglobulin rearrangement, pre-BCR signalling and mature B cell survival. Pax5 regulates B cell lineage commitment by concurrently activating cell specific gene expression as well as suppressing the expression of genes associated with non-B cell fates. The identity of the molecular targets of Pax5-mediated gene repression is the subject of much current interest. Recent studies have documented the essential nature of the Pax5 mediated repression of the stem cell transcriptional program, as well as the silencing of lineage inappropriate gene expression, for B cell development. Surprisingly the repression of genes by Pax5 continues throughout lymphopoiesis, with the loss of Pax5 in mature B cell resulting in the reactivation of the same Pax5 targets during plasma cell differentiation. These recent insights into the mechanism of action of Pax5 in controlling B cell identity will be discussed.
Carotta
Sebastian
S
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Holmes
Melissa L
ML
Pridans
Clare
C
Nutt
Stephen L
SL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008213:Lymphocyte Activation; D008954:Models, Biological; D051757:PAX5 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D010950:Plasma Cells / Q000166:cytology; D015398:Signal Transduction; D014158:Transcription, Genetic
D007136:Immunoglobulins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human