Prak E L, Weigert M
Department of Molecular Biology, Princeton University, New Jersey 08544, USA.
J Exp Med. 1995 Aug 1;182(2):541-8. doi: 10.1084/jem.182.2.541.
A functional B cell antigen receptor is thought to regulate antibody gene rearrangement either by stopping further rearrangement (exclusion) or by promoting additional rearrangement (editing). We have developed a new model to study the regulation of antibody gene rearrangement. In this model, we used gene targeting to replace the J kappa region with a functional V kappa-J kappa light chain gene. Two different strains of mice were created; one, V kappa 4R, has a V kappa 4-J kappa 4 rearrangement followed by a downstream J kappa 5 segment, while the other, V kappa 8R, has a V kappa 8-J kappa 5 light chain. Here, we analyze the influence of these functional light chains on light chain rearrangement. We show that some V kappa 4R and V kappa 8R B cells only have the V kappa R light chain rearrangement, whereas others undergo additional rearrangements. Additional rearrangement can occur not only at the other kappa allele or isotype (lambda), but also at the targeted locus in both V kappa 4R and V kappa 8R. Rearrangement to the downstream J kappa 5 segment is observed in V kappa 4R, as is deletion of the targeted locus in both V kappa 4R and V kappa 8R. The V kappa R models illustrate that a productively rearranged light chain can either terminate further rearrangement or allow further rearrangement. We attribute the latter to editing of autoantibodies and to corrections of dysfunctional receptors.
功能性B细胞抗原受体被认为可通过停止进一步重排（排除）或促进额外重排（编辑）来调节抗体基因重排。我们开发了一种新模型来研究抗体基因重排的调控。在该模型中，我们利用基因靶向技术用功能性Vκ-Jκ轻链基因取代Jκ区域。创建了两种不同品系的小鼠；一种是Vκ4R，具有Vκ4-Jκ4重排，随后是下游的Jκ5片段，而另一种是Vκ8R，具有Vκ8-Jκ5轻链。在此，我们分析这些功能性轻链对轻链重排的影响。我们发现一些Vκ4R和Vκ8R B细胞仅具有VκR轻链重排，而其他细胞则经历额外重排。额外重排不仅可发生在另一个κ等位基因或同种型（λ），也可发生在Vκ4R和Vκ8R的靶向位点。在Vκ4R中观察到重排至下游Jκ5片段，在Vκ4R和Vκ8R中均观察到靶向位点的缺失。VκR模型表明，一个有效重排的轻链既可以终止进一步重排，也可以允许进一步重排。我们将后者归因于自身抗体的编辑和功能失调受体的校正。
