Elsevier

Seminars in Immunology

Volume 10, Issue 2, April 1998, Pages 133-142
Seminars in Immunology

Regular Article
Loss- and gain-of-function mutations reveal an important role of BSAP (Pax-5) at the start and end of B cell differentiation

https://doi.org/10.1006/smim.1998.0115Get rights and content

Abstract

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 α) and N-myc genes as well as in the developmental pathway controlling VH-to-DHJHrecombination 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.

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