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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 composition and surface marker expression of H. pylori-infected subjects compared to healthy controls.(A) Gating strategy for B cells in PBMC. All subsequent populations shown were gated accordingly on CD3-CD19+ live singlet lymphocytes. (B) Representative dot plots depicting IgD vs. CD27, CD27 vs. CD21, and CD38 vs. CD24 expression on B cells in healthy H. pylori-uninfected subjects (H. pylori-uninfected, N = 20), H. pylori-infected non-smoking non-obese asymptomatic (Asymptomatic, N = 15), H. pylori-infected smoking non-obsese (Smoking, N = 15), and H. pylori-infected obese non-smoking (Obese, N = 15) subjects. (C) Percentages of IgD+CD27- naïve B cells, CD21+CD27+ classical memory B cells, and CD24+CD38+ regulatory B cells in study groups. *: P<0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test). For flow cytometry analysis, greater than 106 events in the lymphocyte gate were collected.
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pone.0134591.g001: B cell composition and surface marker expression of H. pylori-infected subjects compared to healthy controls.(A) Gating strategy for B cells in PBMC. All subsequent populations shown were gated accordingly on CD3-CD19+ live singlet lymphocytes. (B) Representative dot plots depicting IgD vs. CD27, CD27 vs. CD21, and CD38 vs. CD24 expression on B cells in healthy H. pylori-uninfected subjects (H. pylori-uninfected, N = 20), H. pylori-infected non-smoking non-obese asymptomatic (Asymptomatic, N = 15), H. pylori-infected smoking non-obsese (Smoking, N = 15), and H. pylori-infected obese non-smoking (Obese, N = 15) subjects. (C) Percentages of IgD+CD27- naïve B cells, CD21+CD27+ classical memory B cells, and CD24+CD38+ regulatory B cells in study groups. *: P<0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test). For flow cytometry analysis, greater than 106 events in the lymphocyte gate were collected.

Mentions: Circulating B cells in the peripheral blood of healthy subjects are composed of mainly IgD+CD27- naïve B cells and CD21+CD27+ resting memory B cells, while in chronic infections, there is frequently a decrease in naïve B cells and resting memory B cells, and an increase in CD21lo activated B cells and CD24+CD38+ B cells[15,18]. We first examined the composition of circulating B cells in H. pylori-infected subjects. Peripheral blood mononuclear cells (PBMCs) were stained for surface marker expression directly ex vivo (Fig 1A). We found that comparing to H. pylori-uninfected healthy subjects, all H. pylori-infected groups contained lower percentages of IgD+CD27- naïve B cells (P<0.001 for all, Fig 1B and 1C). The percentages of CD21+CD27+ resting memory B cells were reduced in H. pylori-infected smoking subjects and obese subjects compared to healthy subjects (P<0.001 for both), and the percentage of CD21+CD27+ B cells in obese subjects was reduced compared to H. pylori-infected asymptomatic subjects (P<0.01). Interestingly, the percentages of CD24+CD38+ B cells were varied among different groups of H. pylori-infected subjects. H. pylori-infected asymptomatic subjects contained much higher percentages of CD24+CD38+ B cells than healthy controls (P<0.001). The percentage of CD24+CD38+ B cells was reduced in smoking subjects compared to that in asymptomatic subjects (P<0.05), but still higher than that in healthy subjects (P<0.001). In obese subjects, the percentage of CD24+CD38+ B cells was not significantly different from that in healthy subjects but was reduced from that in asymptomatic subjects (P<0.001).


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 composition and surface marker expression of H. pylori-infected subjects compared to healthy controls.(A) Gating strategy for B cells in PBMC. All subsequent populations shown were gated accordingly on CD3-CD19+ live singlet lymphocytes. (B) Representative dot plots depicting IgD vs. CD27, CD27 vs. CD21, and CD38 vs. CD24 expression on B cells in healthy H. pylori-uninfected subjects (H. pylori-uninfected, N = 20), H. pylori-infected non-smoking non-obese asymptomatic (Asymptomatic, N = 15), H. pylori-infected smoking non-obsese (Smoking, N = 15), and H. pylori-infected obese non-smoking (Obese, N = 15) subjects. (C) Percentages of IgD+CD27- naïve B cells, CD21+CD27+ classical memory B cells, and CD24+CD38+ regulatory B cells in study groups. *: P<0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test). For flow cytometry analysis, greater than 106 events in the lymphocyte gate were collected.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4520600&req=5

pone.0134591.g001: B cell composition and surface marker expression of H. pylori-infected subjects compared to healthy controls.(A) Gating strategy for B cells in PBMC. All subsequent populations shown were gated accordingly on CD3-CD19+ live singlet lymphocytes. (B) Representative dot plots depicting IgD vs. CD27, CD27 vs. CD21, and CD38 vs. CD24 expression on B cells in healthy H. pylori-uninfected subjects (H. pylori-uninfected, N = 20), H. pylori-infected non-smoking non-obese asymptomatic (Asymptomatic, N = 15), H. pylori-infected smoking non-obsese (Smoking, N = 15), and H. pylori-infected obese non-smoking (Obese, N = 15) subjects. (C) Percentages of IgD+CD27- naïve B cells, CD21+CD27+ classical memory B cells, and CD24+CD38+ regulatory B cells in study groups. *: P<0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test). For flow cytometry analysis, greater than 106 events in the lymphocyte gate were collected.
Mentions: Circulating B cells in the peripheral blood of healthy subjects are composed of mainly IgD+CD27- naïve B cells and CD21+CD27+ resting memory B cells, while in chronic infections, there is frequently a decrease in naïve B cells and resting memory B cells, and an increase in CD21lo activated B cells and CD24+CD38+ B cells[15,18]. We first examined the composition of circulating B cells in H. pylori-infected subjects. Peripheral blood mononuclear cells (PBMCs) were stained for surface marker expression directly ex vivo (Fig 1A). We found that comparing to H. pylori-uninfected healthy subjects, all H. pylori-infected groups contained lower percentages of IgD+CD27- naïve B cells (P<0.001 for all, Fig 1B and 1C). The percentages of CD21+CD27+ resting memory B cells were reduced in H. pylori-infected smoking subjects and obese subjects compared to healthy subjects (P<0.001 for both), and the percentage of CD21+CD27+ B cells in obese subjects was reduced compared to H. pylori-infected asymptomatic subjects (P<0.01). Interestingly, the percentages of CD24+CD38+ B cells were varied among different groups of H. pylori-infected subjects. H. pylori-infected asymptomatic subjects contained much higher percentages of CD24+CD38+ B cells than healthy controls (P<0.001). The percentage of CD24+CD38+ B cells was reduced in smoking subjects compared to that in asymptomatic subjects (P<0.05), but still higher than that in healthy subjects (P<0.001). In obese subjects, the percentage of CD24+CD38+ B cells was not significantly different from that in healthy subjects but was reduced from that in asymptomatic subjects (P<0.001).

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