Kuo F C, Sklar J
Division of Molecular Oncology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Exp Med. 1997 Nov 3;186(9):1547-56. doi: 10.1084/jem.186.9.1547.
B cells that mediate normal, T cell-dependent, humoral immune responses must first pass through germinal centers (GCs) within the cortex of antigenically stimulated lymph nodes. As they move through the dark zone and then the light zone in the GC, B cells are subjected to somatic hypermutation and switch recombination within their rearranged immunoglobulin genes and also participate in a number of other processes that control development into memory cells or cells specialized for antibody secretion. To investigate the molecular mechanisms that contribute to B cell development within GCs, we constructed a recombinant DNA library enriched for cDNAs derived from human genes expressed in B cells at this site. This library was found to contain a cDNA structurally and functionally related to genes in bacteria and yeast for the DNA repair enzyme 8-oxoguanine DNA glycosylase. Northern blot analysis indicated that the human gene is expressed as two alternatively spliced messenger RNAs within GC B cells at levels greatly exceeding that found in other tissues. In situ hybridization studies revealed that expression of this gene is most abundant within the dark zones of GCs. Both the function and localized expression of this gene suggest that it may play a role in somatic hypermutation of immunoglobulin genes.
介导正常的、T细胞依赖性体液免疫反应的B细胞，必须首先穿过抗原刺激淋巴结皮质内的生发中心（GCs）。当B细胞在生发中心的暗区然后是亮区移动时，它们在重排的免疫球蛋白基因内经历体细胞超突变和类别转换重组，并且还参与许多其他控制发育为记忆细胞或专门分泌抗体的细胞的过程。为了研究促成生发中心内B细胞发育的分子机制，我们构建了一个重组DNA文库，该文库富含来自在此位点B细胞中表达的人类基因的cDNA。发现该文库包含一个与细菌和酵母中DNA修复酶8-氧鸟嘌呤DNA糖基化酶的基因在结构和功能上相关的cDNA。Northern印迹分析表明，该人类基因在生发中心B细胞内以两种可变剪接的信使RNA形式表达，其水平大大超过在其他组织中发现的水平。原位杂交研究表明，该基因的表达在生发中心的暗区内最为丰富。该基因的功能和定位表达均表明它可能在免疫球蛋白基因的体细胞超突变中起作用。
