Pax5 determines B- versus T-cell fate and does not block early myeloid-lineage development.
Progenitor B cells deficient in Pax5 are developmentally multipotent, suggesting that Pax5 is necessary to maintain commitment to the B-cell lineage. Commitment may be mediated, in part, by Pax5 repression of myeloid-specific genes. To determine whether Pax5 expression in multipotential cells is sufficient to restrict development to the B-cell lineage in vivo, we enforced expression of Pax5 in hematopoietic stem cells using a retroviral vector. Peripheral blood analysis of all animals reconstituted with Pax5-expressing cells indicated that more than 90% of Pax5-expressing cells were B220+ mature B cells that were not malignant. Further analysis showed that Pax5 completely blocked T-lineage development in the thymus but did not inhibit myelopoiesis or natural killer (NK) cell development in bone marrow. These results implicate Pax5 as a critical regulator of B- versus T-cell developmental fate and suggest that Pax5 may promote commitment to the B-cell lineage by mechanisms that are independent of myeloid gene repression.
Cotta
Claudiu V
CV
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA.
Zhang
Zheng
Z
Kim
Hyung-Gyoon
HG
Klug
Christopher A
CA
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects; D019891:Leukopoiesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D022423:Myeloid Cells / Q000166:cytology* / Q000187:drug effects; D051757:PAX5 Transcription Factor; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D014157:Transcription Factors