Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors.
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.
Rolink
A G
AG
Basel Institute for Immunology, Switzerland. rolink@bii.ch
Nutt
S L
SL
Melchers
F
F
Busslinger
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D002460:Cell Line; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D019891:Leukopoiesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000502:physiology*; D051757:PAX5 Transcription Factor; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C499308:Rag2 protein, mouse; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2