Adult BM generates CD5+ B1 cells containing abundant N-region additions.

Adult BM generates CD5+ B1 cells containing abundant N-region additions.
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DOI:
10.1002/eji.200838920
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发表时间:
2009-09
影响因子:
5.4
通讯作者:
Rothstein, Thomas L.
Rothstein, Thomas L.
中科院分区:
医学3区
文献类型:
--
作者:
Holodick, Nichol E.;Repetny, Karen;Zhong, Xuemei;Rothstein, Thomas L.

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B1细胞的自我更新能力暗示着体内平衡的调节;然而,先前的工作表明,B1细胞早期特征的低水平N区增加随着年龄的增加而增加,这意味着B1细胞群体不是一个封闭的系统。为了探索这一点,我们评估了成人BM产生的CD5+B1细胞的N区添加。用小鼠干细胞病毒转导引入的绿色荧光蛋白标记成人骨髓细胞,然后过继转移到致死性照射的受体体内。在2-3个月内,我们在受体的腹膜腔中发现了GFP标记的CD5+B细胞,我们在这里证明了它们符合B1细胞特征的各种标准,包括Mac-1表面表达;Annexin、Elfin和Pax-5基因表达;对佛波酯的促有丝分裂反应性;以及自发的免疫球蛋白分泌。值得注意的是,我们通过单细胞PCR发现,这群来自BM的CD5+B1细胞表达免疫球蛋白,具有丰富的N区添加(和很少的VH11/VH12偏斜),不同于从未经处理的动物获得的CD5+B1细胞,但使人联想到B2细胞。此外,我们证实了来自老年小鼠的天然CD5+B1细胞比来自年轻小鼠的天然CD5+B1细胞含有更多的N区增加。这些结果表明,随着时间的推移,成年的BM前体细胞有助于腹膜CD5+B1-细胞池的形成。
The self-renewing capacity of B1 cells infers homeostatic regulation; however, previous work suggests the low level of N-region addition characterizing B1 cells early in life increases with age, which implies that the B1-cell population is not a closed system. To explore this, we evaluated N-region addition in CD5+ B1 cells generated from adult BM. Adult BM cells were marked with GFP introduced by mouse stem cell virus transduction, and were then adoptively transferred into lethally irradiated recipients. Within 2–3 months, we found GFP-marked CD5+ B cells in the peritoneal cavities of recipients, which we demonstrate here meet a variety of criteria for B1-cell traits including Mac-1 surface expression; annexin, elfin, and Pax-5 gene expression; mitogenic responsiveness to phorbol ester; and spontaneous immunoglobulin secretion. Notably, we found by single-cell PCR that this population of BM-derived CD5+ B1 cells expressed immunoglobulin with abundant N-region addition (and little VH11/VH12 skewing), unlike CD5+ B1 cells obtained from unmanipulated animals but reminiscent of B2 cells. Further, we confirmed that native CD5+ B1 cells from older mice contain more N-region additions than native CD5+ B1 cells from younger mice. These results suggest that adult BM progenitors contribute to the peritoneal CD5+ B1-cell pool over time.
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