Early generated B1 B cells with restricted BCRs become chronic lymphocytic leukemia with continued c-Myc and low Bmf expression.
Early generated B1 B cells with restricted BCRs become chronic lymphocytic leukemia with continued c-Myc and low Bmf expression.
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具有受限BCR的早期生成的B1 B细胞成为持续C-MYC和低BMF表达的慢性淋巴细胞性白血病。
DOI：
10.1084/jem.20160712
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发表时间：
2016-12-12
期刊：
影响因子：
--
通讯作者：
Hardy RR
中科院分区：
文献类型：
--
作者：
Hayakawa K;Formica AM;Brill-Dashoff J;Shinton SA;Ichikawa D;Zhou Y;Morse HC 3rd;Hardy RR
Hayakawa等人表明，B-1发育的独特B系进展允许产生具有有限BCR和自我更新能力的B1 a细胞，两者都有助于CLL进展的潜力。在小鼠中，胎儿/新生儿B-1 B细胞发育中的（自身）配体暴露诱导的BCR信号传导导致自身反应性CD 5 + B细胞的产生。这些细胞的一部分自我更新，并持续作为一个小的B1 B细胞亚群在整个生命。在这里，我们表明，从Eμ-TCL 1转基因小鼠转移早期产生的B1 B细胞导致慢性淋巴细胞白血病（CLL）与偏见的剧目，包括定型的BCR。因此，携带限制性BCR的B1 B细胞可在老化期间变成CLL。通过转基因表达增加B1 B细胞亚群中的抗胸腺细胞/Thy-1自身反应（ATA）BCR细胞，产生自发ATA B-CLL/淋巴瘤发病率，并通过TCL 1转基因增强。相比之下，ATA B-CLL不从其他B细胞亚群发展，即使当相同的ATA BCR在Thy-1低/空背景下表达时。因此，特定的BCR和B1 B细胞环境对于CLL进展都是重要的。新生儿B1 B细胞及其CLL后代在老年小鼠中继续表达适度上调的c-Myc和下调的促凋亡Bmf，这与成年小鼠中的大多数成熟B细胞不同。因此，在B-1发育中存在固有的遗传倾向，产生受限的BCR和自我更新能力，这两种特征都有助于进展为CLL的潜力。
Hayakawa et al. show that distinctive B-lineage progression from B-1 development allows for generation of B1a cells with restricted BCRs and self-renewal capacity, both contributing to potential for CLL progression. In mice, generation of autoreactive CD5+ B cells occurs as a consequence of BCR signaling induced by (self)-ligand exposure from fetal/neonatal B-1 B cell development. A fraction of these cells self-renew and persist as a minor B1 B cell subset throughout life. Here, we show that transfer of early generated B1 B cells from Eμ-TCL1 transgenic mice resulted in chronic lymphocytic leukemia (CLL) with a biased repertoire, including stereotyped BCRs. Thus, B1 B cells bearing restricted BCRs can become CLL during aging. Increased anti-thymocyte/Thy-1 autoreactive (ATA) BCR cells in the B1 B cell subset by transgenic expression yielded spontaneous ATA B-CLL/lymphoma incidence, enhanced by TCL1 transgenesis. In contrast, ATA B-CLL did not develop from other B cell subsets, even when the identical ATA BCR was expressed on a Thy-1 low/null background. Thus, both a specific BCR and B1 B cell context were important for CLL progression. Neonatal B1 B cells and their CLL progeny in aged mice continued to express moderately up-regulated c-Myc and down-regulated proapoptotic Bmf, unlike most mature B cells in the adult. Thus, there is a genetic predisposition inherent in B-1 development generating restricted BCRs and self-renewal capacity, with both features contributing to potential for progression to CLL.
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影响因子：
12.4
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6.4
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