Department of Pathology and Laboratory of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
Blood. 2010 May 20;115(20):4043-50. doi: 10.1182/blood-2009-09-241638. Epub 2009 Dec 30.
Although the 3 isoforms of Akt regulate cell growth, proliferation, and survival in a wide variety of cell types, their role in B-cell development is unknown. We assessed B-cell maturation in the bone marrow (BM) and periphery in chimeras established with fetal liver progenitors lacking Akt1 and/or Akt2. We found that the generation of marginal zone (MZ) and B1 B cells, 2 key sources of antibacterial antibodies, was highly dependent on the combined expression of Akt1 and Akt2. In contrast, Akt1/2 deficiency did not negatively affect the generation of transitional or mature follicular B cells in the periphery or their precursors in the BM. However, Akt1/2-deficient follicular B cells exhibited a profound survival defect when forced to compete against wild-type B cells in vivo. Altogether, these studies show that Akt signaling plays a key role in peripheral B-cell maturation and survival.
尽管 Akt 的 3 种同工型在多种细胞类型中调节细胞生长、增殖和存活，但它们在 B 细胞发育中的作用尚不清楚。我们在利用缺乏 Akt1 和/或 Akt2 的胎肝祖细胞建立的嵌合体中评估了骨髓 (BM) 和外周血中的 B 细胞成熟情况。我们发现，边缘区 (MZ) 和 B1 B 细胞（两种产生抗菌抗体的关键来源）的产生高度依赖于 Akt1 和 Akt2 的共同表达。相比之下，Akt1/2 缺陷并不对外周血中转渡或成熟滤泡 B 细胞或其 BM 前体的产生产生负面影响。然而，当 Akt1/2 缺陷型滤泡 B 细胞在体内与野生型 B 细胞竞争时，其存活缺陷非常严重。总之，这些研究表明 Akt 信号通路在周围 B 细胞成熟和存活中发挥着关键作用。
