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PLoS One. 2016 Mar 11;11(3):e0150411. doi: 10.1371/journal.pone.0150411. eCollection 2016.

A Gain-Of-Function Mutation in the Plcg2 Gene Protects Mice from Helicobacter felis-Induced Gastric MALT Lymphoma.

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Department of Hematology, Oncology and Immunology, Philipps University of Marburg, and University Hospital Giessen and Marburg, Marburg, Germany.
Institute of Pathology, Kulmbach Hospital, Kulmbach, Germany.
Institute of Medical Microbiology, Philipps University of Marburg, Marburg, Germany.
Institute of Immunology, Philipps University of Marburg, Marburg, Germany.
Institute of Pathology, Philipps University of Marburg, Marburg, Germany.
Institute of Molecular Biology and Tumor Research, Philipps University of Marburg, Marburg, Germany.
Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.


Gastric mucosa-associated lymphoid tissue (MALT) lymphomas develop from a chronic Helicobacter infection. Phospholipase C gamma 2 (PLCG2) is important for B-cell survival and proliferation. We used BALB/c mice with a gain-of-function mutation in the Plcg2 gene (Ali5) to analyze its role in the development of gastric MALT lymphoma. Heterozygous BALB/c Plcg2Ali5/+ and wildtype (WT) mice were infected with Helicobacter felis (H. felis) and observed up to 16 months for development of gastric MALT lymphomas. In contrast to our initial hypothesis, Plcg2Ali5/+ mice developed MALT lymphomas less frequently than their WT littermates after long-term infection of 16 months. Infected Plcg2Ali5/+ mice showed downregulation of proinflammatory cytokines and decreased H. felis-specific IgG1 and IgG2a antibody responses. These results suggested a blunted immune response of Plcg2Ali5/+ mice towards H. felis infection. Intriguingly, Plcg2Ali5/+ mice harboured higher numbers of CD73 expressing regulatory T cells (Tregs), possibly responsible for impaired immune response towards Helicobacter infection. We suggest that Plcg2Ali5/+ mice may be protected from developing gastric MALT lymphomas as a result of elevated Treg numbers, reduced response to H. felis and decrease of proinflammatory cytokines.

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