Antibiotics May Not Be Enough To Stop Recurrent Gastric Lymphoma Caused By Helicobacter Pylori

Helicobacter pylori, a spiral bacterium of the stomach, infects morethan half of the world's population. It is now widely accepted that,aside from gastritis and ulcers, H. pylori is also a causative agent ofgastric lymphoma, specifically gastric B cell lymphoma ofmucosa-associated lymphoid tissue (MALT). While antibiotic treatmenteradicates the bacteria and promotes tumor regression, the effects ofre-infection on disease are more severe.

To address the effects of re-infection and the role of immunecells in disease progression, Dr. Mueller's group used a mouse model ofHelicobacter-induced MALT lymphoma that employs H. felis to mimic humandisease in the mouse. Mice were infected with H. felis and maintainedfor 18 months before being assigned to one of three treatment groups:1) no treatment (primarily infected), 2) antibiotic therapy toeradicate bacteria, or 3) antibiotic therapy followed by re-infection.

As expected, low-grade MALT lymphoma occurred in 35% of allinfected animals. However, frank MALT lymphoma was more prevalent inre-infected animals (44%) than in primarily infected animals (25%).Transcription profiling identified B cell markers in mice that had beeninfected at any point in time, even after successful antibiotictreatment, suggesting that resting B cells remain in the gastricmucosa.

Lymphoid aggregates of re-infected animals also contained moreproliferating cells than those of primarily infected orantibiotic-treated animals (46% vs. 23.2% or 4.8%, respectively).Closer inspection of the lymphoid aggregates revealed that the tumorswere indeed derived from B cells and the main antigen-presenting cellswere follicular dendritic cells. Finally, follicular dendritic cellnumbers were highest in the tumors of re-infected animals followed byprimarily infected and then antibiotic-treated animals, thuscorrelating with severity of gastric lymphoma.

Because it is the follicular dendritic cells that presentantigen to T cells that in turn activate B cell proliferation,follicular dendritic cells appear to be better indicators of tumorbehavior than B cells. Thus, follicular dendritic cells represent anuntapped target in the fight against recurrent gastric lymphoma.

The significance of the described work is that gastriclymphoma progresses more rapidly upon secondary infection. Becauseresting B cells are left behind following antibiotic treatment,re-infection by H. pylori promotes the existing B cells to progressquickly into tumors. Therefore, it is important that treated patientsbe carefully monitored for H. pylori re-infection.

Mueller A, O'Rourke J, Chu P, Chu A, Dixon MF, Bouley DM, Lee A,Falkow S: The role of antigenic drive and tumor-infiltrating accessorycells in the pathogenesis of Helicobacter-induced MALT lymphoma. Am JPathol 2005, 167:797-812

Research was supported by the National Institutes of Health(US), the Emmy-Noether-Program of the Deutsche Forschungsgemeinschaft(Germany), and J National Health and Medical Research Council(Australia).

The American Journal of Pathology, the official journal of theAmerican Society for Investigative Pathology (ASIP), seeks to publishhigh-quality original papers on the cellular and molecular mechanismsof disease. The editors accept manuscripts which report importantfindings on disease pathogenesis or basic biological mechanisms thatrelate to disease, without preference for a specific method ofanalysis. High priority is given to studies on human disease andrelevant experimental models using cellular, molecular, biological,animal, chemical and immunological approaches in conjunction withmorphology.