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

Abstract

Pax5-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 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 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 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. © 2002 by The American Society of Hematology.