title: Pax5: a master regulator of B cell development and leukemogenesis.
abstract: The B cell lineage of the hematopoietic system is responsible for the generation of high-affinity antibodies, which provide humoral immunity for protection against foreign pathogens. B cell commitment and development depend on many transcription factors including Pax5. Here, we review the different functions of Pax5 in regulating various aspects of B lymphopoiesis. At B cell commitment, Pax5 restricts the developmental potential of lymphoid progenitors to the B cell pathway by repressing B-lineage-inappropriate genes, while it simultaneously promotes B cell development by activating B-lymphoid-specific genes. Pax5 thereby controls gene transcription by recruiting chromatin-remodeling, histone-modifying, and basal transcription factor complexes to its target genes. Moreover, Pax5 contributes to the diversity of the antibody repertoire by controlling V(H)-DJ(H) recombination by inducing contraction of the immunoglobulin heavy-chain locus in pro-B cells, which is likely mediated by PAIR elements in the 5' region of the V(H) gene cluster. Importantly, all mature B cell types depend on Pax5 for their differentiation and function. Pax5 thus controls the identity of B lymphocytes throughout B cell development. Consequently, conditional loss of Pax5 allows mature B cells from peripheral lymphoid organs to develop into functional T cells in the thymus via dedifferentiation to uncommitted progenitors in the bone marrow. Pax5 has also been implicated in human B cell malignancies because it can function as a haploinsufficient tumor suppressor or oncogenic translocation fusion protein in B cell precursor acute lymphoblastic leukemia.
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Jasna
authors.initials: J
authors.lastname: Medvedovic
authors.forename: Anja
authors.initials: A
authors.lastname: Ebert
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tagoh
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
mesh_terms: D000818:Animals; D000916:Antibody Diversity; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D005786:Gene Expression Regulation; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007938:Leukemia / Q000276:immunology / Q000473:pathology*; D038041:Lymphopoiesis; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse