CLONAL DELETION OF LYMPHOCYTE-B IN A TRANSGENIC MOUSE BEARING ANTI-MHC CLASS-I ANTIBODY GENES

CLONAL DELETION OF LYMPHOCYTE-B IN A TRANSGENIC MOUSE BEARING ANTI-MHC CLASS-I ANTIBODY GENES
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DOI:
10.1038/337562a0
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发表时间:
1989-02-09
期刊:
影响因子:
64.8
通讯作者:
BURKI, K
BURKI, K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
NEMAZEE, DA;BURKI, K

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通过体内和体外的实验操作,可以使B淋巴细胞对抗原特异性无反应1 -6,但由于B细胞受T淋巴细胞控制,在缺乏T淋巴细胞的情况下,B细胞对抗原的反应很差,因此天然耐受性是否涉及B细胞耐受性仍不清楚(参考文献7)。此外,在正常小鼠中可以发现产生自身抗体的细胞,它们的形成被B细胞有丝分裂原如脂多糖增强8 -12。我们已经研究了B细胞耐受性的转基因小鼠使用IgM抗H-2kMHC I类抗体的基因。在H-2d转基因小鼠中,约25-50%的脾B细胞具有这种特异性的膜免疫球蛋白,并产生大量由转基因编码的血清IgM。相反,H-2 kx H-2 d(H-2-d/k)转基因小鼠缺乏携带抗H-2 kidiotype的B细胞,并且不含可检测的血清抗H-2 k抗体,这表明可以通过克隆缺失来控制非常大量的自身特异性B细胞。
B lymphocytes can be rendered specifically unresponsive to antigen by experimental manipulationin vivoandin vitro1–6, but it remains unclear whether or not natural tolerance involves B-cell tolerance because B cells are controlled by T lymphocytes, and in their absence respond poorly to antigen (reviewed in ref. 7). In addition, autoantibody-producing cells can be found in normal mice and their formation is enhanced by B-cell mitogens such as lipopolysaccharides8–12. We have studied B-cell tolerance in transgenic mice using genes for IgM anti-H–2kMHC class I antibody. In H–2dtransgenic mice about 25–50% of the splenic B cells bear membrane immunoglobulin of this specificity, and abundant serum IgM encoded by the transgenes is produced. In contrast, H–2kx H–2d(H–2-d/k) transgenic mice lack B cells bearing the anti-H–2kidiotype and contain no detectable serum anti-H–2kantibody, suggesting that very large numbers of autospecific B cells can be controlled by clonal deletion.