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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.

Author information

1
Department of Hematology, Oncology and Immunology, Philipps University of Marburg, and University Hospital Giessen and Marburg, Marburg, Germany.
2
Institute of Pathology, Kulmbach Hospital, Kulmbach, Germany.
3
Institute of Medical Microbiology, Philipps University of Marburg, Marburg, Germany.
4
Institute of Immunology, Philipps University of Marburg, Marburg, Germany.
5
Institute of Pathology, Philipps University of Marburg, Marburg, Germany.
6
Institute of Molecular Biology and Tumor Research, Philipps University of Marburg, Marburg, Germany.
7
Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.

Abstract

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.

PMID:
26966907
PMCID:
PMC4788355
DOI:
10.1371/journal.pone.0150411
[Indexed for MEDLINE]
Free PMC Article

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