Enhanced differentiation of splenic plasma cells but diminished long-lived high-affinity bone marrow plasma cells in aged mice
Enhanced differentiation of splenic plasma cells but diminished long-lived high-affinity bone marrow plasma cells in aged mice
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DOI：
10.4049/jimmunol.170.3.1267
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发表时间：
2003-02-01
影响因子：
4.4
通讯作者：
Zheng, B
中科院分区：
文献类型：
--
作者：
Han, SS;Yang, KY;Zheng, B
在目前的工作中，我们已经解剖的机制负责受损的体液反应在老化。我们发现，有一个显着较高水平的抗体形成细胞在老年小鼠的脾脏比年轻的控制。然而，老年小鼠脾脏中高亲和力、类别转换的抗体形成细胞的数量严重减少。老年动物脾脏中低亲和力IgM抗体形成细胞的蓄积不是由于同种型转换的缺陷，因为总IgG1脾浆细胞的数量没有显著减少。值得注意的是，与年轻小鼠相比，老年小鼠骨髓中低亲和力和高亲和力的浆细胞均显著减少。重建实验的结果表明，老年骨髓对来自年轻脾B细胞的浆细胞的支持性较低。这些发现表明，衰老中的体液免疫缺陷至少由两种机制引起：无法产生足够数量的高亲和力抗体形成细胞，这是由于生发中心反应减弱，以及有缺陷的骨髓环境，其支持长期抗体形成细胞的选择和存活的能力减弱。
In the present work, we have dissected the mechanisms responsible for the impaired humoral responses in aging. We found that there was a substantially higher level of Ab-forming cells in the spleens of aged mice than that of young controls. However, the number of high-affinity, class-switched Ab-forming cells was severely decreased in the spleen of aged mice. The accumulation of low-affinity IgM Ab-forming cells in the spleens of aged animals was not due to a deficiency in isotype switching because the number of total IgG1 splenic plasma cells was not significantly reduced. Remarkably, plasma cells of both low and high affinity were significantly diminished in the bone marrow of aged mice compared with that of young mice. The results from reconstitution experiments showed that aged bone marrow was less supportive for plasma cells derived from young splenic B cells. These findings suggest that humoral immune deficiency in aging results from at least two mechanisms: the inability to generate sufficient numbers of high-affinity Ab-forming cells, which is a result of diminished germinal center reaction, and the defective bone marrow environment that has diminished ability to support the selection and survival of long-term Ab-forming cells.