Wardemann Hedda, Hammersen Johanna, Nussenzweig Michel C
The Rockefeller University, 1230 York Ave., Box 220, New York, NY 10021, USA.
J Exp Med. 2004 Jul 19;200(2):191-9. doi: 10.1084/jem.20040818.
Several newly arising human antibodies are polyreactive, but in normal individuals the majority of these potentially autodestructive antibodies are removed from the repertoire by receptor editing or B cell deletion in the bone marrow. To determine what proportion of naturally arising autoantibodies can be silenced by immunoglobulin (Ig) light chain receptor editing, we replaced the light chains in 12 such antibodies with a panel of representative Igkappa and Iglambda chains. We found that most naturally arising autoantibodies are readily silenced by light chain exchange. Thus, receptor editing may account for most autoreactive antibody silencing in humans. Light chain complementarity determining region (CDR) isoelectric points did not correlate with silencing activity, but Iglambda genes were more effective than Igkappa genes as silencers. The greater efficacy of Iglambda chains as silencer of autoreactivity provides a possible explanation for the expansion and altered configuration of the Iglambda locus in evolution.
几种新出现的人类抗体具有多反应性，但在正常个体中，这些潜在的自毁性抗体中的大多数通过受体编辑或骨髓中的B细胞缺失从抗体库中被清除。为了确定天然产生的自身抗体中有多大比例可以通过免疫球蛋白（Ig）轻链受体编辑而沉默，我们用一组代表性的Igκ和Igλ链替换了12种此类抗体中的轻链。我们发现，大多数天然产生的自身抗体很容易通过轻链交换而沉默。因此，受体编辑可能是人类大多数自身反应性抗体沉默的原因。轻链互补决定区（CDR）的等电点与沉默活性无关，但Igλ基因作为沉默剂比Igκ基因更有效。Igλ链作为自身反应性沉默剂的更高效力为Igλ基因座在进化中的扩展和构型改变提供了一种可能的解释。
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