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在小鼠B细胞系中,功能性免疫球蛋白轻链基因被种系Vκ基因与下游Jκ片段的持续重排所取代。

Functional immunoglobulin light chain genes are replaced by ongoing rearrangements of germline V kappa genes to downstream J kappa segment in a murine B cell line.

作者信息

Levy S, Campbell M J, Levy R

机构信息

Department of Medicine, Stanford University School of Medicine, California 94305.

出版信息

J Exp Med. 1989 Jul 1;170(1):1-13. doi: 10.1084/jem.170.1.1.

Abstract

A murine B cell lymphoma (38C13) was subjected to immunoselection with mAbs directed against the idiotypic determinants of its cell surface Ig. Variants emerged with altered Ig receptors containing identical heavy chains but different light chains. The functional light chain genes in these variants were composed of V kappa segments drawn from the V kappa Ox-1 family, which had replaced the V kappa gene expressed by the parental tumor by rearranging to downstream J kappa segments. Rearrangement at the kappa locus continued to occur spontaneously, giving rise to secondary and tertiary variants at a rate of 1.9 x 10(-4) per cell per generation. Variants were isolated that had ceased production of surface Ig but went on to rearrange again and to become surface Ig+. The Ig- state may be an intermediate step providing a stimulus for continued rearrangement. This process provides an additional mechanism for generating diversity within B cell clones and expands the use of the available repertoire of Ig genes.

摘要

一株小鼠B细胞淋巴瘤(38C13)用针对其细胞表面Ig独特型决定簇的单克隆抗体进行免疫选择。出现了具有改变的Ig受体的变体,其含有相同的重链但不同的轻链。这些变体中的功能性轻链基因由来自VκOx-1家族的Vκ片段组成,这些片段通过重排到下游的Jκ片段而取代了亲本肿瘤表达的Vκ基因。κ位点的重排继续自发发生,以每细胞每代1.9×10⁻⁴的速率产生二级和三级变体。分离出了停止产生表面Ig但继续重排并变为表面Ig⁺的变体。Ig⁻状态可能是为持续重排提供刺激的中间步骤。这一过程为在B细胞克隆内产生多样性提供了一种额外机制,并扩展了Ig基因可用库的使用。

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