Positive selection of anti-thy-1 autoreactive B-1 cells and natural serum autoantibody production independent from bone marrow B cell development.

Positive selection of anti-thy-1 autoreactive B-1 cells and natural serum autoantibody production independent from bone marrow B cell development.
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DOI:
10.1084/jem.20021459
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发表时间:
2003-01-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Hardy RR
Hardy RR
中科院分区:
其他
文献类型:
--
作者:
Hayakawa K;Asano M;Shinton SA;Gui M;Wen LJ;Dashoff J;Hardy RR

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一种针对Thy-1糖蛋白的天然血清自身抗体(抗Thy-1自身抗体[ATA])是由自身抗原阳性选择的B-1细胞产生的。在此,利用ATAμκ转基因小鼠,我们发现具有这种B细胞受体的细胞在骨髓发育过程中被负选择。在Thy-1缺失的环境下,脾脏的BM - ATA B细胞进展到正常滤泡期。然而,在自身抗原阳性的环境中,脾脏的发育在未成熟阶段被阻止,同时伴有CD5的诱导。这些细胞具有耐受性,寿命短,与b1细胞不同。尽管如此,ATAμκ小鼠自身抗原依赖的高血清ATA生成表明,ATA阳性选择明显,其占血清免疫球蛋白M的90%。脾切除术不能消除ATA的产生,耐受性脾B细胞的转移也不能诱导ATA的产生。这些发现表明,B-1阳性选择导致天然血清ATA的产生,独立于BM B细胞发育和选择的主要途径。
A natural serum autoantibody specific for the Thy-1 glycoprotein (anti–Thy-1 autoantibody [ATA]) is produced by B-1 cells that are positively selected by self-antigen. Here, using ATAμκ transgenic mice we show that cells with this B cell receptor are negatively selected during bone marrow (BM) development. In a Thy-1 null environment, BM ATA B cells progress to a normal follicular stage in spleen. However, in a self-antigen–positive environment, development is arrested at an immature stage in the spleen, concomitant with induction of CD5. Such cells are tolerant and short-lived, different from B-1. Nonetheless, ATA-positive selection was evident by self-antigen–dependent high serum ATA production, comprising ∼90% of serum immunoglobulin M in ATAμκ mice. Splenectomy did not eliminate ATA production and transfer of tolerant splenic B cells did not induce it. These findings demonstrate that B-1 positive selection, resulting in the production of natural serum ATA, arises independently from the major pathway of BM B cell development and selection.
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发表时间: 1991-12-01
影响因子: 11.1
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