Multiple hematopoietic cell lineages develop in vivo from transplanted Pax5-deficient pre-B I–cell clones

Abstract

AbstractPax5-deficient pre-B I–cell clones, transplanted into natural killer (NK)–cell–deficient RAG2−/−IL-2Rγ−/−hosts, populate the NK-cell compartment with functional NK cells. NK-cell generation fromPax5−/−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 CD8α− and CD8α+ dendritic cells (DCs), macrophages, and granulocytes in vivo in approximately half the hosts. In some recipients, practically all the mature myeloid cells are ofPax5−/− 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.