Varade W S, Insel R A
Department of Pediatrics, University of Rochester Medical Center, New York 14642.
J Clin Invest. 1993 Apr;91(4):1838-42. doi: 10.1172/JCI116397.
12 rearranged human VH6 immunoglobulin heavy chain genes arising from the same rearrangement were isolated without preselection from the RNA of a fragment of human spleen. The 12 clones were isolated from a pool of 31 unique VH6 clones arising from 18 unique rearrangements. 2 of the 12 related clones were expressed with IgM, 2 with IgG, and 8 with IgA1. All the clones, including those expressing IgM, showed extensive somatic mutation of germline bases (5.6%), which was consistent with antigen-driven activation of these VH6-expressing clones with recruitment into the immune repertoire. On the basis of significant sharing of somatic mutations between the IgM clones and clones expressing the other isotypes (six mutations shared with IgG clones and eight mutations shared with IgA clones), it was apparent that the IgM-expressing precursor in this diversified family had undergone extensive antigen-driven somatic mutation prior to isotype switching. This family of related clones suggests that a germinal centerlike event had been sampled. The highly mutated IgM clones suggest that there may exist memory B cells capable of further somatic mutation and differential isotype-switching depending on the specific antigenic stimulus.
从人脾脏片段的RNA中未经预选分离出12个源自相同重排的重排人VH6免疫球蛋白重链基因。这12个克隆是从由18个独特重排产生的31个独特VH6克隆的文库中分离出来的。12个相关克隆中有2个与IgM一起表达，2个与IgG一起表达，8个与IgA1一起表达。所有克隆，包括那些表达IgM的克隆，都显示出种系碱基的广泛体细胞突变（5.6%），这与这些表达VH6的克隆的抗原驱动激活以及进入免疫库一致。基于IgM克隆与表达其他同种型的克隆之间体细胞突变的显著共享（与IgG克隆共享6个突变，与IgA克隆共享8个突变），很明显，这个多样化家族中表达IgM的前体在同种型转换之前已经经历了广泛的抗原驱动体细胞突变。这个相关克隆家族表明已经采样到了类似生发中心的事件。高度突变的IgM克隆表明可能存在能够根据特定抗原刺激进一步进行体细胞突变和差异同种型转换的记忆B细胞。
