Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors

Nature. 1999 Oct 7;401(6753):603-6. doi: 10.1038/44164.


The mechanisms controlling the commitment of haematopoietic progenitors to the B-lymphoid lineage are poorly understood. The observations that mice deficient in E2A and EBF lack B-lineage cells have implicated these two transcription factors in the commitment process. Moreover, the expression of genes encoding components of the rearrangement machinery (RAG1, RAG2, TdT) or pre-B-cell receptor (lambda5, VpreB, Igalpha, Igbeta) has been considered to indicate B-lineage commitment. All these genes including E2A and EBF are expressed in pro-B cells lacking the transcription factor Pax5. Here we show that cloned Pax5-deficient pro-B cells transferred into RAG2-deficient mice provide long-term reconstitution of the thymus and give rise to mature T cells expressing alpha/beta-T-cell receptors. The bone marrow of these mice contains a population of cells of Pax5-/- origin with the same phenotype as the donor pro-B cells. When transferred into secondary recipients, these pro-B cells again home to the bone marrow and reconstitute the thymus. Hence, B-lineage commitment is determined neither by immunoglobulin DJ rearrangement nor by the expression of E2A, EBF, lambda5, VpreB, Igalpha and Igbeta. Instead, our data implicate Pax5 in the control of B-lineage commitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Bone Marrow Cells / physiology
  • Cell Line
  • Clone Cells
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Hematopoietic Stem Cells / physiology*
  • Leukopoiesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nuclear Proteins / physiology*
  • PAX5 Transcription Factor
  • T-Lymphocytes / physiology*
  • Thymus Gland / cytology
  • Transcription Factors*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Rag2 protein, mouse
  • Transcription Factors
  • V(D)J recombination activating protein 2