Low multiplicity of infection of Helicobacter pylori suppresses apoptosis of B lymphocytes

Francoise I. Bussiere, Rupesh Chaturvedi, Mohammad Asim, Kristen L. Hoek, Yulan Cheng, Justin Gainor, Adina Scholz, Wasif N. Khan, Keith T. Wilson

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 MOI. 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.

Original languageEnglish (US)
Pages (from-to)6834-6842
Number of pages9
JournalCancer Research
Volume66
Issue number13
DOIs
StatePublished - Jul 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Bussiere, F. I., Chaturvedi, R., Asim, M., Hoek, K. L., Cheng, Y., Gainor, J., Scholz, A., Khan, W. N., & Wilson, K. T. (2006). Low multiplicity of infection of Helicobacter pylori suppresses apoptosis of B lymphocytes. Cancer Research, 66(13), 6834-6842. https://doi.org/10.1158/0008-5472.CAN-05-4197