Long-term bone marrow cultures provide access to early lymphoid progenitors

Long-term bone marrow cultures provide defined systems for studying and man ipulating hematopoietic progenitors. Myeloid bone marrow cultures harbor ea rly lymphoid progenitors; however, the nature and phenotype of these progen itors has not been investigated. Phenotypic and molecular markers associate d with lymphopoiesis were used to characterize the lymphoid population main tained in these cultures. Cells within myeloid cultures expressed genes ass ociated with lymphopoiesis but did not express the B cell-specific lambda5 gene. Flow cytometry demonstrated that cultures lacked cells expressing mar kers associated with B cell development. Furthermore, rearrangements of imm unoglobulin heavy chain diversity (D) and joining (J(H)) gene segments were not detected in the myeloid cultures suggesting that these conditions supp ort early B cell progenitors. Transferring myeloid cultures to conditions o ptimal for lymphopoiesis resulted in B cell development that temporally rec apitulated events in the bone marrow. We also demonstrate that these lympho id progenitors are targets for retroviral transduction. This study suggests that long-term cultures provide a useful system to access early lymphoid p rogenitors and study the events that regulate their differentiation.