BSAP/Pax5A expression blocks survival and expansion of early myeloid cellsimplicating its involvement in maintaining commitment to the B-lymphocyte lineage

Early B lymphopoiesis is marked by plasticity between the myeloid and B lin eages. An attractive model for B-lineage development is that commitment to this lineage is partly determined by the ordered expression of genes that p rohibit switching to the myeloid lineage. In this regard, whereas the role of the B-cell-specific transcription factor BSAP/Pax5A in regulating B-lymp hoid-restricted gene expression has been well-established. its role in main taining B-lineage commitment is unclear. Thus, BSAP/Pax5A was constitutivel y expressed in the multipotent EML cell line, which can be directed toward the myeloid lineage by culture with interleukin-3 (IL-3) and retinoic acid. EML cells expressing BSAP/ Pax5A successfully acquired the myeloid lineage markers CD11b and F4/80 in response to IL-3 and retinoic acid, indicating differentiation to the myeloid lineage. However, these early myeloid cells failed to expand in culture with granulocyte-macrophage colony-stimulating factor and were directed instead toward an apoptotic pathway. In parallel, primary bane marrow stem cells transduced with retrovirus constitutively ex pressing BSAP/Pax5A began myeloid cell differentiation, but like the transf ormed EML model failed to expand in response to myeloid growth factors. The se studies identify a role for BSAP/Pax5A in suppressing the response to my eloid growth factors, which may be a component of the regulatory processes that limit plasticity of early B-lymphoid progenitors. (C) 1999 by The Amer ican Society of Hematology.