Low multiplicity of infection of Helicobacter pylori suppresses apoptosis of B lymphocytes
Low multiplicity of infection of Helicobacter pylori suppresses apoptosis of B lymphocytes
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DOI：
10.1158/0008-5472.can-05-4197
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发表时间：
2006-07-01
期刊：
影响因子：
11.2
通讯作者：
Wilson, Keith T.
中科院分区：
文献类型：
--
作者：
Bussiere, Francoise I.;Chaturvedi, Rupesh;Wilson, Keith T.
幽门螺杆菌感染的人的胃引起慢性胃炎，可导致胃癌。由于激活的淋巴细胞在胃粘膜中持续存在，并且由于H。pylori感染诱导细胞凋亡，我们推测淋巴细胞对凋亡的抵抗是对H.幽门。新鲜分离的小鼠脾细胞发生大量自发性凋亡，并对H. pylori感染，低MOI（1-10）明显抑制细胞凋亡，而高MOI（>= 75）则增强细胞凋亡。低MOI减少线粒体膜去极化，caspase-3和caspase-9激活，细胞色素c释放和Bcl-2水平增加。低MOI也诱导细胞增殖。当细胞与H. pylori感染时，CD 19（+）B细胞在低MOI下可免于凋亡并进行增殖，而CD 3（+）T细胞则不表现出这种模式。即使在活化前分离B细胞，低MOI对凋亡的保护作用也持续存在。免疫表型分析显示，所有B细胞亚群在低MOL时均未发生凋亡。pylori可保护脾B细胞免于自发凋亡。我们的研究结果表明，低水平的H。体内发生的幽门螺杆菌感染与B细胞存活和增殖相关，这与它们演变成粘膜相关淋巴组织淋巴瘤的潜力一致。
Helicobacter pylori infection of the human stomach causes chronic gastritis that can lead to gastric cancer. Because activated lymphocytes persist in the gastric mucosa, and because a high multiplicity of infection (MOI) of H. pylori is needed to induce apoptosis in vitro, we speculated that resistance of lymphocytes to apoptosis is an important feature of the immune response to H. pylori. Freshly isolated mouse splenocytes underwent substantial spontaneous apoptosis and displayed a biphasic response to H. pylori, in which low MOI (1-10) markedly inhibited apoptosis, whereas high MOI ( >= 75) potentiated apoptosis. Low MOI reduced mitochondrial membrane depolarization, caspase-3 and caspase-9 activation, and cytochrome c release and increased Bcl-2 levels. Low MOI also induced cellular proliferation. When cells were subjected to fluorescence-activated cell sorting after coculture with H. pylori, CD19(+) B cells were found to be protected from apoptosis and undergoing proliferation at low MOI, whereas CD3(+) T cells did not exhibit this pattern. The protective effect of low MOI on apoptosis persisted even when B cells were isolated before activation. Immunophenotyping showed that all B-cell subsets examined were protected from apoptosis at low MOL Additionally, gastric infection with H. pylori resulted in protection of splenic B cells from spontaneous apoptosis. Our results suggest that the low levels of H. pylori infection that occur in vivo are associated with B-cell survival and proliferation, consistent with their potential to evolve into mucosa-associated lymphoid tissue lymphoma.