A B-cell receptor-specific selection step governs immature to mature B cell differentiation

A B-cell receptor-specific selection step governs immature to mature B cell differentiation
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DOI:
10.1073/pnas.050552997
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发表时间:
2000-03-14
影响因子:
11.1
通讯作者:
Shlomchik, MJ
Shlomchik, MJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Levine, MH;Haberman, AM;Shlomchik, MJ

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70%的外周未成熟常规(BZ)B细胞不能发育成成熟B细胞,这种细胞损失的性质尚未被表征;控制哪些未成熟B细胞发育成长寿外周B细胞的过程可以是随机的或选择性的。在这里,我们证明了这一步实际上是选择性的,因为未成熟的B细胞的命运高度依赖于其Ig受体的特异性。当细胞进入成熟B细胞部分时,发生B细胞受体库的显著偏斜,这表明只有少数未成熟B细胞被选择成为成熟B细胞。因为只有少数重链-轻链对在多样的可用库中增强,所以我们赞成这样的想法,即选择对这些少数重链-轻链对是阳性的,而不是对几乎所有其他重链-轻链对是阴性的。因为大多数未成熟的B细胞在该转变时丢失,所以该推定的阳性选择事件可能是形成可用于适应性免疫应答的成熟B细胞受体库的主要力量。
Seventy percent of peripheral immature conventional (BZ) B cells fail to develop into mature B cells, The nature of this cell loss has not been characterized; the process that governs which immature B cells develop into long-lived peripheral B cells could be either stochastic or selective. Here, we demonstrate that this step is in fact selective, in that the fate of an immature B cell is highly dependent on its lg receptor specificity. A significant skewing of the B cell receptor repertoire occurs by the time cells enter the mature B cell fraction, which indicates that there is selection of only a minority of immature B cells to become mature B cells. Because only a few heavy-light chain pairs are enhanced of the diverse available repertoire, we favor the idea that selection is positive for these few heavy-light chain pairs rather than negative against nearly all others. Because most immature B cells are lost at this transition, this putative positive selection event is likely to be a major force shaping the mature B cell receptor repertoire available for adaptive immune responses.