Liu Y J, de Bouteiller O, Arpin C, Brière F, Galibert L, Ho S, Martinez-Valdez H, Banchereau J, Lebecque S
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Immunity. 1996 Jun;4(6):603-13. doi: 10.1016/s1074-7613(00)80486-0.
Somatic hypermutation in immunoglobulin variable region genes occurs within germinal centers. Here, we describe a subset of germinal center dark zone centroblasts that express only sIgD and have accumulated up to 80 mutations per heavy chain variable region (IgVH delta gene). Over half of the hypermutated IgVH delta sequences were found to be clonally related. This level of mutation is not observed in either IgVH gamma transcripts from the same sample or IgVH delta transcripts from peripheral blood, suggesting that these cells neither undergo isotype switch nor mature into circulating memory B cells. Optimal growth of these cells in vitro depends on CD40 ligand, T cell cytokines, and a fibroblast stroma, a combination possibly mimicking the dark zone microenvironment. Our hypothesis is that these cells may be sequestered within germinal centers, where their somatic mutation machinery is triggered. The isolation of these hypermutated B cells may represent a critical step for studying both the biology and biochemistry of somatic hypermutation.
免疫球蛋白可变区基因的体细胞高频突变发生在生发中心内。在此，我们描述了生发中心暗区中心母细胞的一个亚群，这些细胞仅表达sIgD，并且每个重链可变区（IgVHδ基因）积累了多达80个突变。发现超过一半的高频突变IgVHδ序列是克隆相关的。在来自同一样本的IgVHγ转录本或外周血的IgVHδ转录本中均未观察到这种突变水平，这表明这些细胞既不发生同种型转换，也不成熟为循环记忆B细胞。这些细胞在体外的最佳生长取决于CD40配体、T细胞细胞因子和成纤维细胞基质，这种组合可能模拟了暗区微环境。我们的假设是，这些细胞可能被隔离在生发中心内，在那里它们的体细胞突变机制被触发。这些高频突变B细胞的分离可能代表了研究体细胞高频突变生物学和生物化学的关键步骤。
