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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

CD24+CD38+ B cell responses to bacterial antigen stimulation in different study groups.Total B cells were isolated from PBMCs by negative selection and then cultured in the absence or presence of heat-killed H. pylori bacterium, together with IL-10 capture beads. After 72h incubation, the secretion of IL-10 in the supernatant was collected by capture beads and measured by luminex assay. The B cells were also harvested for intracellular IL-10 staining. N = 8 for every group. (A) Secreted IL-10 concentration in the supernatant. (B) Percentage of IL-10+ cells in CD24+CD38+ B cells at the end of the 72h incubation. *: P< 0.05. **: P<0.01. ***: P<0.001. (Student’s t test).
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pone.0134591.g004: CD24+CD38+ B cell responses to bacterial antigen stimulation in different study groups.Total B cells were isolated from PBMCs by negative selection and then cultured in the absence or presence of heat-killed H. pylori bacterium, together with IL-10 capture beads. After 72h incubation, the secretion of IL-10 in the supernatant was collected by capture beads and measured by luminex assay. The B cells were also harvested for intracellular IL-10 staining. N = 8 for every group. (A) Secreted IL-10 concentration in the supernatant. (B) Percentage of IL-10+ cells in CD24+CD38+ B cells at the end of the 72h incubation. *: P< 0.05. **: P<0.01. ***: P<0.001. (Student’s t test).

Mentions: We next sought to examine the mechanism of IL-10 upregulation in the B cells of H. pylori-infected subjects. IL-10 production is pivotal to regulatory B cell function[12,13]. Toll-like receptor signaling is a major IL-10 upregulation mechanism in B cells, and was shown to modulate cytokine expression in H. pylori infection[22,23]. We tested whether the presence of H. pylori can directly upregulate IL-10 secretion in CD24+CD38+ B cells. Purified B cells from PBMCs were cultured in the absence or presence of heat-killed H. pylori bacterium. After 72h incubation, the secretion of IL-10 in the supernatant was measured by luminex. The B cells were also harvested for intracellular IL-10 staining. As shown in Fig 4A, IL-10 secretion in the supernatant is increased in both H. pylori-uninfected healthy subjects and H. pylori-infected non-smoking non-obese asymptomatic subjects after H. pylori-stimulation (P<0.01 and P<0.05, respectively). Fig 4B shows that the percentage of IL-10-secreting B cells was upregulated in CD24+CD38+ B cells after H. pylori stimulation in healthy and asymptomatic subjects (P<0.001 and P<0.05, respectively). In contrast, the concentration of IL-10 in the supernatant and the percentage of IL-10-producing CD24+CD38+ B cells from H. pylori-infected smoking subjects and obese subjects were not significantly increased after H. pylori-infection. These data demonstrated that smoking and obesity had impaired the induction of IL-10 from B cells after H. pylori stimulation, and suggested that in part, the loss of regulatory function of CD24+CD38+ B cells from smoking subjects and obese subjects was possibly due to an inability to upregulate IL-10 secretion in response to bacterial antigen stimulation (See discussion).


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)

CD24+CD38+ B cell responses to bacterial antigen stimulation in different study groups.Total B cells were isolated from PBMCs by negative selection and then cultured in the absence or presence of heat-killed H. pylori bacterium, together with IL-10 capture beads. After 72h incubation, the secretion of IL-10 in the supernatant was collected by capture beads and measured by luminex assay. The B cells were also harvested for intracellular IL-10 staining. N = 8 for every group. (A) Secreted IL-10 concentration in the supernatant. (B) Percentage of IL-10+ cells in CD24+CD38+ B cells at the end of the 72h incubation. *: P< 0.05. **: P<0.01. ***: P<0.001. (Student’s t test).
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pone.0134591.g004: CD24+CD38+ B cell responses to bacterial antigen stimulation in different study groups.Total B cells were isolated from PBMCs by negative selection and then cultured in the absence or presence of heat-killed H. pylori bacterium, together with IL-10 capture beads. After 72h incubation, the secretion of IL-10 in the supernatant was collected by capture beads and measured by luminex assay. The B cells were also harvested for intracellular IL-10 staining. N = 8 for every group. (A) Secreted IL-10 concentration in the supernatant. (B) Percentage of IL-10+ cells in CD24+CD38+ B cells at the end of the 72h incubation. *: P< 0.05. **: P<0.01. ***: P<0.001. (Student’s t test).
Mentions: We next sought to examine the mechanism of IL-10 upregulation in the B cells of H. pylori-infected subjects. IL-10 production is pivotal to regulatory B cell function[12,13]. Toll-like receptor signaling is a major IL-10 upregulation mechanism in B cells, and was shown to modulate cytokine expression in H. pylori infection[22,23]. We tested whether the presence of H. pylori can directly upregulate IL-10 secretion in CD24+CD38+ B cells. Purified B cells from PBMCs were cultured in the absence or presence of heat-killed H. pylori bacterium. After 72h incubation, the secretion of IL-10 in the supernatant was measured by luminex. The B cells were also harvested for intracellular IL-10 staining. As shown in Fig 4A, IL-10 secretion in the supernatant is increased in both H. pylori-uninfected healthy subjects and H. pylori-infected non-smoking non-obese asymptomatic subjects after H. pylori-stimulation (P<0.01 and P<0.05, respectively). Fig 4B shows that the percentage of IL-10-secreting B cells was upregulated in CD24+CD38+ B cells after H. pylori stimulation in healthy and asymptomatic subjects (P<0.001 and P<0.05, respectively). In contrast, the concentration of IL-10 in the supernatant and the percentage of IL-10-producing CD24+CD38+ B cells from H. pylori-infected smoking subjects and obese subjects were not significantly increased after H. pylori-infection. These data demonstrated that smoking and obesity had impaired the induction of IL-10 from B cells after H. pylori stimulation, and suggested that in part, the loss of regulatory function of CD24+CD38+ B cells from smoking subjects and obese subjects was possibly due to an inability to upregulate IL-10 secretion in response to bacterial antigen stimulation (See discussion).

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