Outbred mice with long-term Helicobacter felis infection develop both gastric lymphoid tissue and glandular hyperplastic lesions

J Pathol. 2000 Jul;191(3):333-40. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH619>3.0.CO;2-H.


Experimental infection of mice with Helicobacter felis reproduces many aspects of the gastritis observed in Helicobacter pylori-infected humans. The development of gastric inflammatory lesions in chronically infected inbred mice is host-dependent; in BALB/c mice, gastric B-cell MALT lymphomas were observed, whilst other murine hosts (e.g. C57BL/6) developed severe glandular hyperplasia. The aims of this investigation were to characterize and immunophenotype Helicobacter-induced inflammatory lesions in mice with an outbred genetic background. Swiss mice (n=10 per group) were either inoculated with a suspension of H. felis or left untreated. H. felis-inoculated mice and age-matched control animals were killed 13 months later. The severity of gastric inflammatory lesions in the animals was graded and the number and distribution of B (CD45R(+)) and T (CD3(+)) lymphocytes in lymphoid tissues was determined by immunohistochemistry. Compared with control mice, animals with long-term H. felis infection developed severe hyperplastic gastritis (0.80+/-0.63 vs. 2.7+/-0.68), with epithelial dedifferentiation (0. 40+/-0.52 vs. 2.3+/-0.82) and lengthening of the pits and glands (0. 46+/-0.05 vs. 0.8+/-0.19). Gastric CD45R(+) and CD3(+) lymphocyte scores were significantly elevated (r=0.803) in infected animals, while lymphoepithelial lesions and polymorphonuclear leucocyte infiltrates were absent. Although prominent lymphoid follicles were present in the tissues of all infected animals, and in one control animal, only a proportion (55%) of the mucosal follicles had a dominant B-cell phenotype (defined as > or =75% CD45R(+) labelling), and all were poorly labelled with anti-mouse immunoglobulin antibodies. It was concluded that the lesions in outbred Swiss mice differed from B-cell MALT lymphomas. In contrast to inbred mice, outbred animals developed both glandular and lymphoid tissue lesions to chronic H. felis infection. It is suggested that the default T-helper phenotype of the host influences glandular lesion formation or B-cell lymphomagenesis in this model of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology
  • CD3 Complex / analysis
  • Chronic Disease
  • Gastritis / immunology
  • Gastritis / microbiology*
  • Gastritis / pathology
  • Helicobacter Infections / immunology
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology*
  • Hyperplasia / immunology
  • Hyperplasia / microbiology
  • Hyperplasia / pathology
  • Immunoenzyme Techniques
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Leukocyte Common Antigens / analysis
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / microbiology
  • Lymphoid Tissue / pathology*
  • Lymphoma, B-Cell, Marginal Zone / microbiology
  • Mice
  • Species Specificity
  • Specific Pathogen-Free Organisms
  • Stomach / immunology
  • Stomach / microbiology
  • Stomach / pathology*
  • T-Lymphocytes, Helper-Inducer / immunology


  • CD3 Complex
  • Immunoglobulin A
  • Immunoglobulin G
  • Leukocyte Common Antigens