Pax5: a master regulator of B cell development and leukemogenesis

Adv Immunol. 2011;111:179-206. doi: 10.1016/B978-0-12-385991-4.00005-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibody Diversity
  • Antibody Formation
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology
  • Gene Expression Regulation
  • Gene Rearrangement, B-Lymphocyte
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Leukemia / immunology
  • Leukemia / pathology*
  • Lymphopoiesis
  • PAX5 Transcription Factor / genetics
  • PAX5 Transcription Factor / metabolism*


  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • Pax5 protein, mouse