Deviation of the B cell pathway in senescent mice is associated with reduced surrogate light chain expression and altered immature B cell generation, phenotype, and light chain expression.
Deviation of the B cell pathway in senescent mice is associated with reduced surrogate light chain expression and altered immature B cell generation, phenotype, and light chain expression.
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DOI：
10.4049/jimmunol.182.1.138
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Riley RL
中科院分区：
文献类型：
--
作者：
Alter-Wolf S;Blomberg BB;Riley RL
老年小鼠的B淋巴细胞生成的特征是B细胞前体减少和抗体库改变。这可能部分是由于衰老B细胞前体中替代轻链减少和preBCR检查点受损所致。在此，我们发现，老年小鼠保持了一个通常较小的池早期c-kit+前B细胞，表明穷人的前BCR表达，即使前BCR能力的早期前B细胞显着减少。因此，在老年小鼠中，B2 B淋巴细胞生成从依赖于前BCR扩增和选择转向更多的前BCR缺陷途径。来自年轻或老年小鼠的B2 c-kit+ B细胞前体在体外产生新的B细胞，其偏向于更大的尺寸、更高水平的CD 43和降低的κ轻链表达。值得注意的是，老化骨髓中的未成熟B细胞在体内表现出相似的表型。我们推测替代轻链表达的减少有助于老年小鼠前B细胞的减少。B2途径被部分阻断，B细胞发育受限，前BCR表达和信号传导减少。在老年人中，B2途径具有有限的替代轻链，并且越来越多地产生具有改变的表型和轻链表达的新B细胞。
B lymphopoiesis in aged mice is characterized by reduced B cell precursors and an altered antibody repertoire. This likely results, in part, from reduced surrogate light chains in senescent B cell precursors and compromised preBCR checkpoints. Herein, we show that aged mice maintain an ordinarily minor pool of early c-kit+ pre-B cells, indicative of poor preBCR expression, even as preBCR competent early pre-B cells are significantly reduced. Therefore, in aged mice, B2 B lymphopoiesis shifts from dependency on preBCR expansion and selection to more preBCR deficient pathways. B2 c-kit+ B cell precursors, from either young or aged mice, generate new B cells in vitro that are biased to larger size, higher levels of CD43, and decreased κ light chain expression. Notably, immature B cells in aged bone marrow exhibit a similar phenotype in vivo. We hypothesize that reduced surrogate light chain expression contributes to decreased pre-B cells in aged mice. The B2 pathway is partially blocked with limited B cell development and reduced preBCR expression and signaling. In old age, B2 pathways have limited surrogate light chain and increasingly generate new B cells with altered phenotype and light chain expression.
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前体B细胞受体依赖性B细胞增殖和分化不需要骨髓或胎儿肝脏环境。
DOI：
10.1084/jem.191.1.23
发表时间：
2000-01-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
Riley, RL
影响因子：
4.3
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通讯作者：
Longo, DL
影响因子：
4.4
作者：
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通讯作者：
JONGSTRA, J