Multiple hematopoietic cell lineages develop in vivo from transplanted Pax5-deficient pre-B I-cell clones.
Pax5-deficient pre-B I-cell clones, transplanted into natural killer (NK)-cell-deficient RAG2(-/-) IL-2Rgamma(-/-) hosts, populate the NK-cell compartment with functional NK cells. NK-cell generation from Pax5(-/-) pre-B I cells is also observed in NK-cell-proficient Balb/c RAG2(-/-) hosts. In the same Balb/c RAG2(-/-) hosts, Pax5(-/-) pre-B I-cell clones not only populate the pre-B I-cell compartment and fill the deficient T-cell-lineage compartment in the thymus and the periphery of all hosts, as shown before, they also generate CD8alpha(-) and CD8alpha(+) dendritic cells (DCs), macrophages, and granulocytes in vivo in approximately half the hosts. In some recipients, practically all the mature myeloid cells are of Pax5(-/-) origin, indicating the effectiveness by which Pax5(-/-) pre-B I cells can compete with endogenous myeloid precursors. In a smaller percentage of hosts, the generation of Pax5(-/-) pre-B I-cell-derived erythrocytes is observed 4 to 6 months after transplantation. The results indicate that Pax5(-/-) pre-B I cells can develop in vivo in hosts that have undergone transplantation to erythroid, myeloid, and lymphoid cell lineages. Hence, the Pax5(-/-) mutation introduces an unusual instability of differentiation in pre-B I cells so that they appear to dedifferentiate as far back as the pluripotent hematopoietic stem cell.
Schaniel
Christoph
C
Basel Institute for Immunology, Switzerland.
Bruno
Ludovica
L
Melchers
Fritz
F
Rolink
Antonius G
AG
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D002999:Clone Cells / Q000637:transplantation*; D003601:Cytotoxicity Tests, Immunologic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology; D004912:Erythrocytes / Q000166:cytology; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007153:Immunologic Deficiency Syndromes / Q000473:pathology / Q000628:therapy; D053631:Interleukin Receptor Common gamma Subunit; D007694:Killer Cells, Natural / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D051757:PAX5 Transcription Factor; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C499308:Rag2 protein, mouse; D020395:Receptors, Interleukin-7; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2