Meffre E, Milili M, Blanco-Betancourt C, Antunes H, Nussenzweig M C, Schiff C
Laboratory of Molecular Immunology, The Rockefeller University, Howard Hughes Medical Institute, New York, New York, USA.
J Clin Invest. 2001 Sep;108(6):879-86. doi: 10.1172/JCI13051.
Developing B cells must pass a series of checkpoints that are regulated by membrane-bound Ig(mu) through the Igalpha-Igbeta 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 Igkappa and Iglambda 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 Igkappa repertoire in Ig(mu)-deficient pro-B cells was skewed to downstream Jkappas and upstream Vkappas, 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.
正在发育的B细胞必须通过一系列由膜结合型Ig（μ）通过Igalpha - Igbeta信号转导分子调控的检查点。为了确定Ig（μ）表达如何影响人类B细胞发育和抗体选择，我们分析了两名无法产生Ig（μ）蛋白的患者前B细胞中的Ig基因重排。我们发现Ig（μ）表达不影响V（H）、D或J（H）片段的使用，并且人类Igκ和Igλ重组或表达不需要它。然而，前B细胞中发现的重链和轻链与外周B细胞中的不同，因为它们显示出异常长的互补决定区3（CDR3）。此外，Ig（μ）缺陷前B细胞中的Igκ库偏向于下游Jκ和上游Vκ，这与持续的继发性V（D）J重排一致。因此，前B细胞中的继发性V（D）J重组不需要Ig（μ）表达。然而，B细胞受体表达塑造了人类的抗体库，并且对于筛选出具有长CDR3的抗体至关重要。
