A Gain-Of-Function Mutation in the Plcg2 Gene Protects Mice from Helicobacter felis-Induced Gastric MALT Lymphoma
Open accessAbstract
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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In Ali5 heterozygous point mutation, gain-of-function PLCγ2 mice, PLCγ2 protects mice from developing gastric MALT lymphoma in a model of Helicobacter felis infection.
“The use of the Ali5 heterozygous point mutation, gain-of-function PLCγ2 mice (106) in a model of Helicobacter felis infection showed PLCγ2 protects mice from developing gastric MALT lymphoma (138).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [138]
These Ali5 PLCγ2 mice also had decreased levels of inflammatory cytokines and antibody responses to H. felis.
“These mice also had decreased levels of inflammatory cytokines and antibody responses to H. felis, suggesting a weakened immune response after infection that the authors ventured was due to the increased presence of regulatory T cells (138).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [138]
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- Authors
- Gossmann, J., Stolte, M., Lohoff, M., Yu, P., Moll, R., Finkernagel, F., Garn, H., Brendel, C., Bittner, A., Neubauer, A., & Huynh, M. Q.
- Affiliations
- Philipps University of Marburg (DE)
- Corresponding author
- Neubauer, Andreas
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-03-11
- Volume
- 11
- Issue
- 3
- Pages
- e0150411
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4788355
- OpenAlex
- W2464280864
- Cited by
- 11
- References
- 54
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2016: 2
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (SFB‐TR22, /14-2)
- José Carreras Leukämie-Stiftung (AH 06-01)
- Uniklinikum Giessen und Marburg (AH 06-01)
- Topics
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- PLCγ2, gain-of-function mutations, gastric MALT lymphoma, Helicobacter felis, Helicobacter infection, regulatory T cells, CD73, inflammatory cytokines, antibody response, B cell signaling
- MeSH terms
- Animals, Gene Expression Regulation, Immunoglobulin G, Mice, Inbred BALB C, Mutation, Stomach Neoplasms, Cytokines, Helicobacter Infections, Lymphoma, B-Cell, Marginal Zone, Helicobacter felis, T-Lymphocytes, Regulatory, Mice, Phospholipase C gamma
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