title: A Gain-Of-Function Mutation in the Plcg2 Gene Protects Mice from Helicobacter felis-Induced Gastric MALT Lymphoma.
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.
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University of Marburg, and University Hospital Giessen and Marburg, Marburg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gossmann
authors.affiliation: Institute of Pathology, Kulmbach Hospital, Kulmbach, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Stolte
authors.affiliation: Institute of Medical Microbiology, Philipps University of Marburg, Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lohoff
authors.affiliation: Institute of Immunology, Philipps University of Marburg, Marburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Yu
authors.affiliation: Institute of Pathology, Philipps University of Marburg, Marburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Moll
authors.affiliation: Institute of Molecular Biology and Tumor Research, Philipps University of Marburg, Marburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Finkernagel
authors.affiliation: Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University of Marburg, and University Hospital Giessen and Marburg, Marburg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Brendel
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University of Marburg, and University Hospital Giessen and Marburg, Marburg, Germany.
authors.forename: Alwina
authors.initials: A
authors.lastname: Bittner
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University of Marburg, and University Hospital Giessen and Marburg, Marburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Neubauer
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University of Marburg, and University Hospital Giessen and Marburg, Marburg, Germany.
authors.forename: Minh Q
authors.initials: MQ
authors.lastname: Huynh
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000235:genetics* / Q000276:immunology / Q000662:veterinary; D044922:Helicobacter felis / Q000472:pathogenicity*; D007074:Immunoglobulin G / Q000378:metabolism; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000276:immunology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D051966:Phospholipase C gamma / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology / Q000821:virology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D051966:Phospholipase C gamma