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B-cell development fails in the absence of the Pbx1 proto-oncogene.

Pbx1, a homeodomain transcription factor that was originally identified as the product of a proto-oncogene in acute pre-B-cell leukemia, is a global regulator of embryonic development. However, embryonic lethality in its absence has prevented an assessment of its role in B-cell development. Here, using Rag1-deficient blastocyst complementation assays, we demonstrate that Pbx1 null embryonic stem (ES) cells fail to generate common lymphoid progenitors (CLPs) resulting in a complete lack of B and NK cells, and a partial impairment of T-cell development in chimeric mice. A critical role for Pbx1 was confirmed by rescue of B-cell development from CLPs following restoration of its expression in Pbx1-deficient ES cells. In adoptive transfer experiments, B-cell development from Pbx1-deficient fetal liver cells was also severely compromised, but not erased, since transient B lymphopoiesis was detected in Rag-deficient recipients. Conditional inactivation of Pbx1 in pro-B (CD19(+)) cells and thereafter revealed that Pbx1 is not necessary for B-cell development to proceed from the pro-B-cell stage. Thus, Pbx1 critically functions at a stage between hematopoietic stem cell development and B-cell commitment and, therefore, is one of the earliest-acting transcription factors that regulate de novo B-lineage lymphopoiesis.

Pubmed ID: 17244677

Authors

  • Sanyal M
  • Tung JW
  • Karsunky H
  • Zeng H
  • Selleri L
  • Weissman IL
  • Herzenberg LA
  • Cleary ML

Journal

Blood

Publication Data

May 15, 2007

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI047458
  • Agency: NCI NIH HHS, Id: CA42971
  • Agency: NCI NIH HHS, Id: CA90735
  • Agency: NICHD NIH HHS, Id: HD43997

Mesh Terms

  • Animals
  • B-Lymphocytes
  • Blastocyst
  • Chimera
  • Gene Expression Regulation, Developmental
  • Genes, RAG-1
  • Hematopoietic Stem Cells
  • Homeodomain Proteins
  • Liver
  • Lymphopoiesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Transcription Factors