Pax5 determines B- versus T-cell fate and does not block early myeloid-lineage development
Pax5 determines B- versus T-cell fate and does not block early myeloid-lineage development
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DOI：
10.1182/blood-2002-10-3139
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发表时间：
2003-06-01
期刊：
影响因子：
20.3
通讯作者：
Klug, CA
中科院分区：
文献类型：
--
作者：
Cotta, CV;Zhang, Z;Klug, CA
缺乏Pax5的祖细胞是发育多能的，这表明Pax5对于维持B细胞谱系的承诺是必要的。承诺可能部分通过Pax5对骨髓特异性基因的抑制来介导。为了确定Pax5在多潜能细胞中的表达是否足以在体内限制b细胞谱系的发育，我们使用逆转录病毒载体在造血干细胞中强制表达Pax5。用pax5表达细胞重组的所有动物的外周血分析表明，90%以上的pax5表达细胞是B220（+）成熟的B细胞，并且不是恶性的。进一步分析表明，Pax5完全阻断胸腺t谱系的发育，但不抑制骨髓生成或自然杀伤（NK）细胞的发育。这些结果暗示Pax5是b细胞与t细胞发育命运的关键调节因子，并表明Pax5可能通过独立于髓细胞基因抑制的机制促进b细胞谱系的承诺。(C) 2003年由美国血液病学会出版。
Progenitor B cells deficient in Pax5 are developmentally multipotent, suggesting that Pax5 is necessary to maintain commitment to the B-cell lineage. Commitment may be mediated, in part, by Pax5 repression of myeloid-specific genes. To determine whether Pax5 expression in multipotential cells is sufficient to restrict development to the B-cell lineage in vivo, we enforced expression of Pax5 in hematopoietic stem cells using a retroviral vector. Peripheral blood analysis of all animals reconstituted with Pax5-expressing cells indicated that more than 90% of Pax5-expressing cells were B220(+) mature B cells that were not malignant. Further analysis showed that Pax5 completely blocked T-lineage development in the thymus but did not inhibit myelopoiesis or natural killer (NK) cell development in bone marrow. These results implicate Pax5 as a critical regulator of B-versus T-cell developmental fate and suggest that Pax5 may promote commitment to the B-cell lineage by mechanisms that are independent of myelold gene repression. (C) 2003 by The American Society of Hematology.