B-cell-specific coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation
B-cell-specific coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation
复制标题
DOI：
10.1038/383538a0
复制
发表时间：
1996-10-10
期刊：
影响因子：
64.8
通讯作者：
Matthias, P
中科院分区：
文献类型：
--
作者：
Schubart, DB;Rolink, A;Matthias, P
被称为OCT结合因子(OBF)-1、OCA-B或Bob1(参考文献13)的B淋巴细胞特异性转录因子被认为通过在OCT-1或OCT-2的介导下重新聚集到免疫球蛋白启动子的高度保守的八聚体位点而参与免疫球蛋白基因的转录。为了确定OBP-1在体内的作用，我们在胚胎干细胞中使用了基因打靶技术来产生缺乏辅活化子OBP-1的小鼠。这种OBF-1(-/-)小鼠出生正常，生育能力强，看起来很健康，令人惊讶的是，免疫球蛋白基因的重排和转录基本上没有受到影响。然而，OBF-1基因缺陷的小鼠成熟B细胞数量减少，循环B细胞数量严重减少，但其他情况下表现出正常的B细胞分化。血清中的免疫球蛋白A，特别是免疫球蛋白抗体水平大大降低。如果用胸腺非依赖型或胸腺依赖型抗原免疫突变小鼠，它们的免疫反应会显著减弱。引人注目的是，在胸腺依赖抗原免疫后，生发中心完全不能发育。我们的结果表明，在体内，OBF-1不是免疫球蛋白基因的初始转录所必需的，也不是B细胞发育所必需的，而是B细胞对抗原的反应所必需的，并且是生发中心形成所必需的。
THE B-lymphocyte-specific transcriptional factor called Oct binding factor (OBF)-1, OCA-B or Bob1 (refs 13) is thought to be involved in the transcription of immunoglobulin genes through recruitment to the highly conserved octamer site of immunoglobulin promoters, mediated by either Oct-1 or Oct-2. To define the in vivo role of OBP-1 we have used gene targeting in embryonic stem cells to generate mice lacking the coactivator OBP-1. Such OBF-1(-/-) mice are born normally, are fertile and seem healthy, and surprisingly, rearrangement and transcription of immunoglobulin genes are largely unaffected. However, mice deficient in OBF-1 have reduced numbers of mature B cells and a severe reduction in the number of recirculating B cells, but otherwise show normal B-cell differentiation. Serum IgA and particularly IgG levels are greatly reduced. If mutant mice are immunized with either a thymus-independent or a thymus-dependent antigen, their immune responses are dramatically weakened. Strikingly, germinal centres completely fail to develop after immunization with thymus-dependent antigen. Our results demonstrate that in vivo OBF-1 is not required for initial transcription of immunoglobulin genes or for B cell development, but instead is essential for the response of B cells to antigens, and is required for the formation of germinal centres.