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.
Highlights
Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal marginal zone B-cell lymphomas
We investigated whether a gain-of-function mutation in the Plcg2 gene may have an effect on mucosa-associated lymphoid tissue (MALT) lymphoma development after infection with H. felis
At the end of the experiment, we found that repeated infection with H. felis resulted in increased incidence of MALT lymphomas in both genotypes (83% Plcg2Ali5/+ mice vs. 100% WT mice) (Fishers exact test p = 1)
Summary
Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal marginal zone B-cell lymphomas. There is a strong association between Helicobacter pylori (H. pylori) infection and PLOS ONE | DOI:10.1371/journal.pone.0150411. Reduced MALT Lymphoma Development in Plcg2Ali Mice. AH06-01, to AN); Behring-Röntgen-Stiftung (TP3, 510057, to AN and fellowship, 600.000., to ML; http:// www.br-stiftung.de). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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