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Regulatory B Cell Function Is Suppressed by Smoking and Obesity in H. pylori-Infected Subjects and Is Correlated with Elevated Risk of Gastric Cancer.

Li G, Wulan H, Song Z, Paik PA, Tsao ML, Goodman GM, MacEachern PT, Downey RS, Jankowska AJ, Rabinowitz YM, Learch TB, Song DZ, Yuan JJ, Zheng S, Zheng Z - PLoS ONE (2015)

Bottom Line: We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients.Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects.Regulatory functions mediated by CD24+CD38+ B cells were also impaired.

View Article: PubMed Central - PubMed

Affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Command, Beijing, 100700, China.

ABSTRACT
Helicobacter pylori infection occurs in more than half of the world's population and is the main cause for gastric cancer. A series of lifestyle and nutritional factors, such as tobacco smoking and obesity, have been found to elevate the risk for cancer development. In this study, we sought to determine the immunological aspects during H. pylori infection and gastric cancer development. We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients. IL-10-expressing CD24+CD38+ B cells were upregulated in H. pylori-infected patients, contained potent regulatory activity in inhibiting T cell pro-inflammatory cytokine secretion, and responded directly to H. pylori antigen stimulation. Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects. Regulatory functions mediated by CD24+CD38+ B cells were also impaired. In addition, gastric cancer positive patients had reduced IL-10-producing B cell frequencies after H. pylori-stimulation. Altogether, these data suggest that in H. pylori-infection, CD24+CD38+ B cell is upregulated and plays a role in suppressing pro-inflammatory responses, possibly through IL-10 production, a feature that was not observed in smoking and obese patients.

No MeSH data available.


Related in: MedlinePlus

B cell cytokine expression in H. pylori-infected subjects and in healthy controls.(A) Percentages of total B cells expressing IL-2, IFN-g, TNF-a, and TGF-b in H. pylori-uninfected (N = 7), H.pylori-infected asymptomatic (N = 8), H. pylori-infected smoking (N = 6), and H. pylori-infected obese (N = 6) subjects under unstimulated (without PMA/ionomycin) condition. (B) Representative dot plots of B cell intracellular cytokine staining without or with PMA/ionomycin stimulation, from an uninfected subject. The cytokine expressions of total B cells minus CD24+CD38+ B cells (non-CD24+CD38+ B cells) and that of CD24+CD38+ B cells were shown separately. (C) Percentages of IL-10-expressing, non-CD24+CD38+ B cells and CD24+CD38+ B cells in all study groups, under both unstimulated and PMA/ionomycin stimulated conditions. (D) Numbers of IL-10+ B cells in study groups, calculated by the percentage of IL-10-expressing cells in CD24+CD38+ B cells multiplied by the percentage of CD24+CD38+ in total B cells (as shown in Fig 1C). *: P< 0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test). For dot plots, 5000 events in each gate were shown.
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pone.0134591.g002: B cell cytokine expression in H. pylori-infected subjects and in healthy controls.(A) Percentages of total B cells expressing IL-2, IFN-g, TNF-a, and TGF-b in H. pylori-uninfected (N = 7), H.pylori-infected asymptomatic (N = 8), H. pylori-infected smoking (N = 6), and H. pylori-infected obese (N = 6) subjects under unstimulated (without PMA/ionomycin) condition. (B) Representative dot plots of B cell intracellular cytokine staining without or with PMA/ionomycin stimulation, from an uninfected subject. The cytokine expressions of total B cells minus CD24+CD38+ B cells (non-CD24+CD38+ B cells) and that of CD24+CD38+ B cells were shown separately. (C) Percentages of IL-10-expressing, non-CD24+CD38+ B cells and CD24+CD38+ B cells in all study groups, under both unstimulated and PMA/ionomycin stimulated conditions. (D) Numbers of IL-10+ B cells in study groups, calculated by the percentage of IL-10-expressing cells in CD24+CD38+ B cells multiplied by the percentage of CD24+CD38+ in total B cells (as shown in Fig 1C). *: P< 0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test). For dot plots, 5000 events in each gate were shown.

Mentions: Previously, B cells were found to amplify or suppress immune responses through the production of a series of cytokines with different functions, including pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, IFN-g and TNF-a, as well as IL-10 and transforming growth factor beta (TGF-b) as regulatory cytokines[19]. Here, we examined the cytokine expression of B cells in study subjects. We found that the ex vivo expression of IL-2, IFN-g and TNF-a by B cells were increased in H. pylori-infected smoking subjects and obese subjects than that in healthy subjects (Fig 2A). No significant differences were found in TGF-b expression.


Regulatory B Cell Function Is Suppressed by Smoking and Obesity in H. pylori-Infected Subjects and Is Correlated with Elevated Risk of Gastric Cancer.

Li G, Wulan H, Song Z, Paik PA, Tsao ML, Goodman GM, MacEachern PT, Downey RS, Jankowska AJ, Rabinowitz YM, Learch TB, Song DZ, Yuan JJ, Zheng S, Zheng Z - PLoS ONE (2015)

B cell cytokine expression in H. pylori-infected subjects and in healthy controls.(A) Percentages of total B cells expressing IL-2, IFN-g, TNF-a, and TGF-b in H. pylori-uninfected (N = 7), H.pylori-infected asymptomatic (N = 8), H. pylori-infected smoking (N = 6), and H. pylori-infected obese (N = 6) subjects under unstimulated (without PMA/ionomycin) condition. (B) Representative dot plots of B cell intracellular cytokine staining without or with PMA/ionomycin stimulation, from an uninfected subject. The cytokine expressions of total B cells minus CD24+CD38+ B cells (non-CD24+CD38+ B cells) and that of CD24+CD38+ B cells were shown separately. (C) Percentages of IL-10-expressing, non-CD24+CD38+ B cells and CD24+CD38+ B cells in all study groups, under both unstimulated and PMA/ionomycin stimulated conditions. (D) Numbers of IL-10+ B cells in study groups, calculated by the percentage of IL-10-expressing cells in CD24+CD38+ B cells multiplied by the percentage of CD24+CD38+ in total B cells (as shown in Fig 1C). *: P< 0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test). For dot plots, 5000 events in each gate were shown.
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pone.0134591.g002: B cell cytokine expression in H. pylori-infected subjects and in healthy controls.(A) Percentages of total B cells expressing IL-2, IFN-g, TNF-a, and TGF-b in H. pylori-uninfected (N = 7), H.pylori-infected asymptomatic (N = 8), H. pylori-infected smoking (N = 6), and H. pylori-infected obese (N = 6) subjects under unstimulated (without PMA/ionomycin) condition. (B) Representative dot plots of B cell intracellular cytokine staining without or with PMA/ionomycin stimulation, from an uninfected subject. The cytokine expressions of total B cells minus CD24+CD38+ B cells (non-CD24+CD38+ B cells) and that of CD24+CD38+ B cells were shown separately. (C) Percentages of IL-10-expressing, non-CD24+CD38+ B cells and CD24+CD38+ B cells in all study groups, under both unstimulated and PMA/ionomycin stimulated conditions. (D) Numbers of IL-10+ B cells in study groups, calculated by the percentage of IL-10-expressing cells in CD24+CD38+ B cells multiplied by the percentage of CD24+CD38+ in total B cells (as shown in Fig 1C). *: P< 0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test). For dot plots, 5000 events in each gate were shown.
Mentions: Previously, B cells were found to amplify or suppress immune responses through the production of a series of cytokines with different functions, including pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, IFN-g and TNF-a, as well as IL-10 and transforming growth factor beta (TGF-b) as regulatory cytokines[19]. Here, we examined the cytokine expression of B cells in study subjects. We found that the ex vivo expression of IL-2, IFN-g and TNF-a by B cells were increased in H. pylori-infected smoking subjects and obese subjects than that in healthy subjects (Fig 2A). No significant differences were found in TGF-b expression.

Bottom Line: We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients.Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects.Regulatory functions mediated by CD24+CD38+ B cells were also impaired.

View Article: PubMed Central - PubMed

Affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Command, Beijing, 100700, China.

ABSTRACT
Helicobacter pylori infection occurs in more than half of the world's population and is the main cause for gastric cancer. A series of lifestyle and nutritional factors, such as tobacco smoking and obesity, have been found to elevate the risk for cancer development. In this study, we sought to determine the immunological aspects during H. pylori infection and gastric cancer development. We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients. IL-10-expressing CD24+CD38+ B cells were upregulated in H. pylori-infected patients, contained potent regulatory activity in inhibiting T cell pro-inflammatory cytokine secretion, and responded directly to H. pylori antigen stimulation. Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects. Regulatory functions mediated by CD24+CD38+ B cells were also impaired. In addition, gastric cancer positive patients had reduced IL-10-producing B cell frequencies after H. pylori-stimulation. Altogether, these data suggest that in H. pylori-infection, CD24+CD38+ B cell is upregulated and plays a role in suppressing pro-inflammatory responses, possibly through IL-10 production, a feature that was not observed in smoking and obese patients.

No MeSH data available.


Related in: MedlinePlus