Functionality of Clonal Lymphoid Progenitor Cells Expressing the P210 BCR/ABL Oncogene

Abstract

We have developed an in vitro system in which clonal progenitor cell lines which express the P210 BCR/ABL oncogene and are committed to the B cell lineage can be derived from murine bone marrow and maintained in culture. These cells retain immunoglobulin heavy and light chain genes in a predominantly germline configuration. They express high levels of TdT and sterile u transcripts and undergo diverse DJ rearrangements at the Ig heavy chain locus in vitro. Although growth stimulated by BCR/ABL, the progenitor cells retain full differentiative capacity in vivo. Transfer of these cells to immunodeficient SCID mice leads to reconstitution of functional B cells which respond in a specific fashion to both T-independent and T-dependent antigens and which display diverse V_H family utilization. Tumors have not been observed in the reconstituted mice for at least 60 days. This system demonstrates that P210 can growth stimulate an early progenitor cell without preventing differentiation and should be useful for studying both the B cell developmental process and leukemogenesis.