Immunoglobulin heavy chain expression shapes the B cell receptor repertoire in human B cell development
Immunoglobulin heavy chain expression shapes the B cell receptor repertoire in human B cell development
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DOI：
10.1172/jci13051
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发表时间：
2001-09-01
影响因子：
15.9
通讯作者：
Schiff, C
中科院分区：
文献类型：
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作者：
Meffre, E;Milili, M;Schiff, C
发育中的B细胞必须通过一系列检查点，这些检查点由膜结合的Ig mu通过Ig α -Ig β信号转导器调节。为了确定Ig mu表达如何影响人类B细胞发育和Ab选择，我们分析了来自两名不能产生Ig mu蛋白的患者的前B细胞中的Ig基因重排。我们发现Ig mu的表达不影响V-H、D或J(H)片段的使用，也不是人类Ig kappa和Ig lambda重组或表达所必需的。然而，在前B细胞中发现的重链和轻链与外周B细胞不同，它们表现出异常长的CDR3s。此外，Ig mu缺陷的前b细胞中的Ig kappa曲目向下游的J kappa和上游的V kappa倾斜，这与持续的继发性V(D)J重排一致。因此，在前b细胞中，继发性V(D)J重组不需要Ig mu的表达。然而，B细胞受体的表达塑造了人类的Ab库，并且对于选择具有长CDR3s的Ab至关重要。
Developing B cells must pass a series of checkpoints that are regulated by membrane-bound Ig mu through the Ig alpha -Ig beta signal transducers. To determine how Ig mu expression affects B cell development and Ab selection in humans we analyzed Ig gene rearrangements in pro-B cells from two patients who are unable to produce Ig mu proteins. We find that Ig mu expression does not affect V-H, D, or J(H) segment usage and is not required for human Ig kappa and Ig lambda recombination or expression. However, the heavy and light chains found in pro-B cells differed from those in peripheral B cells in that they showed unusually long CDR3s. In addition, the Ig kappa repertoire in Ig mu -deficient pro-B cells was skewed to downstream J kappas and upstream V kappas, consistent with persistent secondary V(D)J rearrangements. Thus, Ig mu expression is not required for secondary V(D)J recombination in pro-B cells. However, B cell receptor expression shapes the Ab repertoire in humans and is essential for selection against Ab's with long CDR3s.