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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

T cell cytokine secretion after co-culturing with autologous whole B cells, CD24+CD38+-depleted B cells, or CD24+CD38+ B cells.Pure B cells and T cells were isolated from whole PBMCs through magnetic negative selection. Purified B cells were stained with anti-human CD24 and anti-human CD38 antibodies and sent for live cell sorting. The whole B cells, CD24+CD38+-depleted B cells, or purified CD24+CD38+ B cells were then co-cultured with autologous T cells in vitro at 1-to-1 ratio for 72h, after which T cells were further separated through magnetic selection into CD4+ and CD8+ fractions and cultured in the presence of plate-bound anti-CD3 antibody and cytokine capture beads for 6 days. N = 8 for each group. The cytokine productions from (A) CD4+ T cells and (B) CD8+ T cells were then measured by sensitive luminex assay. *: P< 0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test).
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pone.0134591.g003: T cell cytokine secretion after co-culturing with autologous whole B cells, CD24+CD38+-depleted B cells, or CD24+CD38+ B cells.Pure B cells and T cells were isolated from whole PBMCs through magnetic negative selection. Purified B cells were stained with anti-human CD24 and anti-human CD38 antibodies and sent for live cell sorting. The whole B cells, CD24+CD38+-depleted B cells, or purified CD24+CD38+ B cells were then co-cultured with autologous T cells in vitro at 1-to-1 ratio for 72h, after which T cells were further separated through magnetic selection into CD4+ and CD8+ fractions and cultured in the presence of plate-bound anti-CD3 antibody and cytokine capture beads for 6 days. N = 8 for each group. The cytokine productions from (A) CD4+ T cells and (B) CD8+ T cells were then measured by sensitive luminex assay. *: P< 0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test).

Mentions: Regulatory B cells were known to inhibit T cell responses in chronic infections, such as hepatitis B infection and human immunodeficiency virus infection[14,20], by establishing tolerogenic environment through IL-10 prior to the induction of inflammation[15,21]. We examined whether the IL-10-producing CD24+CD38+ B cells had similar regulatory effects in H. pylori-infection. CD4+ T cells co-cultured with autologous CD24+CD38+-depleted B cells had significantly elevated production of IL-2, IL-17, IFN-g and TNF-a, than CD4+ T cells cocultured with whole B cells, in H. pylori-infected asymptomatic patients (Fig 3A). In smoking subjects and obese subjects, such effect was not observed. Similarly, CD8+ T cells from H. pylori-infected asymptomatic subjects co-cultured with autologous CD24+CD38+-depleted B cells significantly enhanced IFN-g and TNF-a secretion than those co-cultured with whole B cells (Fig 3B). Again, such effect was not observed in smoking subjects and obese subjects. The suppression of T cell cytokine expression seems to be mediated by CD24+CD38+ B cells, since lowest cytokine production was observed in CD4+ and CD8+ T cells co-cultured with CD24+CD38+ B cells alone. Altogether, these data demonstrated that the CD24+CD38+ B cells in H. pylori-infected subjects suppressed CD4+ and CD8+ T cell pro-inflammatory cytokine production in H. pylori-infected asymptomatic subjects. Smoking and obesity inhibited regulatory actions of CD24+CD38+ B cells.


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)

T cell cytokine secretion after co-culturing with autologous whole B cells, CD24+CD38+-depleted B cells, or CD24+CD38+ B cells.Pure B cells and T cells were isolated from whole PBMCs through magnetic negative selection. Purified B cells were stained with anti-human CD24 and anti-human CD38 antibodies and sent for live cell sorting. The whole B cells, CD24+CD38+-depleted B cells, or purified CD24+CD38+ B cells were then co-cultured with autologous T cells in vitro at 1-to-1 ratio for 72h, after which T cells were further separated through magnetic selection into CD4+ and CD8+ fractions and cultured in the presence of plate-bound anti-CD3 antibody and cytokine capture beads for 6 days. N = 8 for each group. The cytokine productions from (A) CD4+ T cells and (B) CD8+ T cells were then measured by sensitive luminex assay. *: P< 0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520600&req=5

pone.0134591.g003: T cell cytokine secretion after co-culturing with autologous whole B cells, CD24+CD38+-depleted B cells, or CD24+CD38+ B cells.Pure B cells and T cells were isolated from whole PBMCs through magnetic negative selection. Purified B cells were stained with anti-human CD24 and anti-human CD38 antibodies and sent for live cell sorting. The whole B cells, CD24+CD38+-depleted B cells, or purified CD24+CD38+ B cells were then co-cultured with autologous T cells in vitro at 1-to-1 ratio for 72h, after which T cells were further separated through magnetic selection into CD4+ and CD8+ fractions and cultured in the presence of plate-bound anti-CD3 antibody and cytokine capture beads for 6 days. N = 8 for each group. The cytokine productions from (A) CD4+ T cells and (B) CD8+ T cells were then measured by sensitive luminex assay. *: P< 0.05. **: P<0.01. ***: P<0.001. (Kruskal-Wallis one-way ANOVA and Dunn’s test).
Mentions: Regulatory B cells were known to inhibit T cell responses in chronic infections, such as hepatitis B infection and human immunodeficiency virus infection[14,20], by establishing tolerogenic environment through IL-10 prior to the induction of inflammation[15,21]. We examined whether the IL-10-producing CD24+CD38+ B cells had similar regulatory effects in H. pylori-infection. CD4+ T cells co-cultured with autologous CD24+CD38+-depleted B cells had significantly elevated production of IL-2, IL-17, IFN-g and TNF-a, than CD4+ T cells cocultured with whole B cells, in H. pylori-infected asymptomatic patients (Fig 3A). In smoking subjects and obese subjects, such effect was not observed. Similarly, CD8+ T cells from H. pylori-infected asymptomatic subjects co-cultured with autologous CD24+CD38+-depleted B cells significantly enhanced IFN-g and TNF-a secretion than those co-cultured with whole B cells (Fig 3B). Again, such effect was not observed in smoking subjects and obese subjects. The suppression of T cell cytokine expression seems to be mediated by CD24+CD38+ B cells, since lowest cytokine production was observed in CD4+ and CD8+ T cells co-cultured with CD24+CD38+ B cells alone. Altogether, these data demonstrated that the CD24+CD38+ B cells in H. pylori-infected subjects suppressed CD4+ and CD8+ T cell pro-inflammatory cytokine production in H. pylori-infected asymptomatic subjects. Smoking and obesity inhibited regulatory actions of CD24+CD38+ B cells.

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