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Commitment to the B-lymphoid lineage depends on the transcription factor Pax5

Author

Listed:
  • Stephen L. Nutt

    (Research Institute of Molecular Pathology
    Wellcome/CRC Institute)

  • Barry Heavey

    (Research Institute of Molecular Pathology)

  • Antonius G. Rolink

    (Basel Institute for Immunology)

  • Meinrad Busslinger

    (Research Institute of Molecular Pathology)

Abstract

The Pax5 gene encoding the B-cell-specific activator protein (BSAP) is expressed within the haematopoietic system exclusively in the B-lymphoid lineage, where it is required in vivo for progression beyond the pro-B-cell stage. However, Pax5 is not essential for in vitro propagation of pro-B cells in the presence of interleukin-7 and stromal cells. Here we show that pro-B cells lacking Pax5 are also incapable of in vitro B-cell differentiation unless Pax5 expression is restored by retroviral transduction. Pax5-/- pro-B cells are not restricted in their lineage fate, as stimulation with appropriate cytokines induces them to differentiate into functional macrophages, osteoclasts, dendritic cells, granulocytes and natural killer cells. As expected for a clonogenic haematopoietic progenitor with lymphomyeloid developmental potential, the Pax5-/- pro-B cell expresses genes of different lineage-affiliated programmes, and restoration of Pax5 activity represses this lineage-promiscuous transcription. Pax5 therefore plays an essential role in B-lineage commitment by suppressing alternative lineage choices.

Suggested Citation

  • Stephen L. Nutt & Barry Heavey & Antonius G. Rolink & Meinrad Busslinger, 1999. "Commitment to the B-lymphoid lineage depends on the transcription factor Pax5," Nature, Nature, vol. 401(6753), pages 556-562, October.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6753:d:10.1038_44076
    DOI: 10.1038/44076
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    Cited by:

    1. Qiang Shan & Xiang Li & Xia Chen & Zhouhao Zeng & Shaoqi Zhu & Kexin Gai & Weiqun Peng & Hai-Hui Xue, 2021. "Tcf1 and Lef1 provide constant supervision to mature CD8+ T cell identity and function by organizing genomic architecture," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    2. Chen Chen & Bongsoo Park & Emeline Ragonnaud & Monica Bodogai & Xin Wang & Le Zong & Jung-Min Lee & Isabel Beerman & Arya Biragyn, 2022. "Cancer co-opts differentiation of B-cell precursors into macrophage-like cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Robin D. Lee & Sarah A. Munro & Todd P. Knutson & Rebecca S. LaRue & Lynn M. Heltemes-Harris & Michael A. Farrar, 2021. "Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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