Mikkola Ingvild, Heavey Barry, Horcher Markus, Busslinger Meinrad
Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Science. 2002 Jul 5;297(5578):110-3. doi: 10.1126/science.1067518.
The transcription factor Pax5 is essential for initiating B cell lineage commitment, but its role in maintaining commitment is unknown. Using conditional Pax5 inactivation in committed pro-B cells, we demonstrate that Pax5 is required not only to initiate its B lymphoid transcription program, but also to maintain it in early B cell development. As a consequence of Pax5 inactivation, previously committed pro-B cells regained the capacity to differentiate into macrophages in vitro and to reconstitute T cell development in vivo in RAG2-/- mice. Hence, Pax5 expression is continuously required to maintain B cell lineage commitment, because its loss converts committed pro-B cells into hematopoietic progenitors with multilineage potential.
转录因子Pax5对于启动B细胞谱系定向分化至关重要，但其在维持该定向分化中的作用尚不清楚。通过在已定向的前B细胞中进行条件性Pax5失活，我们证明Pax5不仅是启动其B淋巴细胞转录程序所必需的，而且在早期B细胞发育过程中维持该程序也必不可少。由于Pax5失活，先前已定向的前B细胞在体外重新获得了分化为巨噬细胞的能力，并在RAG2-/-小鼠体内重新构建了T细胞发育过程。因此，持续需要Pax5表达来维持B细胞谱系定向分化，因为其缺失会将已定向的前B细胞转化为具有多谱系分化潜能的造血祖细胞。
