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-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.