DNA and a CpG oligonucleotide derived from Babesia bovis are mitogenic for bovine B cells
DNA and a CpG oligonucleotide derived from Babesia bovis are mitogenic for bovine B cells
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DOI：
10.1128/iai.66.11.5423-5432.1998
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发表时间：
1998-11-01
影响因子：
3.1
通讯作者：
Suarez, CE
中科院分区：
文献类型：
--
作者：
Brown, WC;Estes, DM;Suarez, CE
来自细菌和各种非脊椎动物生物的DNA，包括线虫、软体动物、酵母和昆虫，可引起小鼠B淋巴细胞的多克隆激活。牛B细胞的类似研究尚未报道，迄今为止还没有研究报道任何物种的原生动物DNA的有丝分裂特性。然而，我们和其他人已经观察到原虫寄生虫抗原可以诱导非暴露供体的淋巴细胞增殖。扩展这些研究，我们现在表明，原生动物抗原制剂的有丝分裂特性部分归因于寄生虫DNA，牛巴贝斯虫DNA直接对牛B细胞有丝分裂，牛巴贝斯虫提取物的DNA酶处理消除了牛巴贝斯虫诱导的未暴露牛外周血单个核细胞的增殖。与来自其他生物的DNA对小鼠B细胞具有有丝分裂性一样，B、牛的DNA在很大程度上是非甲基化的，并诱导牛B细胞的剂量依赖性增殖，甲基化后增殖减少。此外，B、牛和大肠杆菌的DNA增强了培养的B细胞的免疫球蛋白分泌，诱导免疫球蛋白GI的适度增加和免疫球蛋白G2的强烈增加。由于已知细菌DNA中存在的某些非甲基化CpG基序可以刺激小鼠和人类B细胞的增殖，因此对牛B DNA的Il-kb片段进行了CG二核苷酸含量和以CG蛾为中心的已知免疫刺激序列（ISS）的分析，发现CG二核苷酸的频率约为预期频率的一半，并鉴定了几个已知具有小鼠B细胞活性的CpG六聚体序列。含有其中一种ISS （AACGTT）的寡脱氧核苷酸，存在于弓形虫相关蛋白-1 （rap-1）开放阅读框中，被证明可以刺激b细胞增殖，这些ISS可能参与原虫感染期间的宿主免疫调节，可能用作疫苗佐剂。
DNAs from bacteria and variety of nonvertebrate organisms, including nematodes, mollusks, yeasts, and insects, cause polyclonal activation of murine: B lymphocytes, Similar studies have not been reported for bovine B cells, and to date no studies have reported mitogenic properties of protozoal DNA for any species. However, we and others have observed that protozoal parasite antigens can induce the proliferation of lymphocytes from nonexposed donors. Extending these studies, we now show that the mitogenic property of protozoal antigen preparations is in part attributable to parasite DNA and that Babesia bovis DNA is directly mitogenic for bovine B cells, DNase treatment of B. bovis extracts abrogated B. bovis-induced proliferation of peripheral blood mononuclear cells from nonexposed cattle. Like DNAs from other organisms that were mitogenic for murine B cells, B, bovis DNA is largely nonmethylated and induced a dose-dependent proliferation of bovine B cells, which was reduced upon methylation, Furthermore, B. bovis and E. coli DNAs enhanced immunoglobulin secretion by cultured B cells, inducing moderate increases in immunoglobulin GI and stronger increases in immunoglobulin G2, Because certain nonmethylated CpG motifs present in bacterial DNA are known to stimulate proliferation of murine and human B cells, in Il-kb fragment of B. bovis DNA was analyzed for CG dinucleotide content and for the presence of known immunostimulatory sequences (ISS) centered on a CG moth, The frequency of CG dinucleotides was approximately one-half of the expected frequency, and several CpG hexameric sequences with known activity for murine B cells were identified. An oligodeoxynucleotide containing one of these ISS (AACGTT), which: is present within the rhoptry-associated protein-1 (rap-1) open reading frame, was shown to stimulate B-cell proliferation, These ISS may be involved in host immune modulation during protozoal infection and may be useful as vaccine adjuvants.