Loss- and gain-of-function mutations reveal an important role of BSAP (Pax-5) at the start and end of B cell differentiation.
Pax-5 codes for the transcription factor BSAP which is expressed throughout B cell development except in terminally differentiated plasma cells. Gene targeting experiments in the mouse revealed a differential dependency of fetal and adult B-lymphopoiesis on this transcription factor. BSAP is required for B-lineage commitment in the fetal liver and for progression beyond an early pro-B cell stage in adult bone marrow. The characterization of Pax-5-deficient pro-B cells demonstrated an important role of BSAP in the regulation of the CD19, mb-1 (Ig alpha) and N-myc genes as well as in the developmental pathway controlling VH-to-DHJH recombination at the immunoglobulin heavy-chain (IgH) locus. The human PAX-5 gene was recently shown to participate together with the IgH locus in the chromosomal translocation t(9;14)(p13;q32). This translocation is characteristic of a small subset of non-Hodgkin lymphomas exhibiting plasmacytoid differentiation. The translocated PAX-5 gene is deregulated by the insertion of IgH regulatory elements into its 5' region, which may contribute to tumorigenesis by interfering with the shut-down of PAX-5 transcription and thus with the completion of plasma cell differentiation.
Morrison
A M
AM
Research Institute of Molecular Pathology, Vienna, Austria.
Nutt
S L
SL
Thévenin
C
C
Rolink
A
A
Busslinger
M
M
D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D019891:Leukopoiesis / Q000502:physiology*; D008099:Liver / Q000196:embryology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D051757:PAX5 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; D014157:Transcription Factors