title: Regulatory B Cell Function Is Suppressed by Smoking and Obesity in H. pylori-Infected Subjects and Is Correlated with Elevated Risk of Gastric Cancer.
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.
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Command, Beijing, 100700, China.
authors.forename: Guanggang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Plastic and Reconstructive Surgery, PLA General Hospital, Beijing, 100853, China.
authors.forename: Hasi
authors.initials: H
authors.lastname: Wulan
authors.affiliation: Department of Oncology, The 155th Central Hospital of PLA, Kaifeng, 475003, China.
authors.forename: Zongchang
authors.initials: Z
authors.lastname: Song
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Paik
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, United States of America.
authors.forename: Ming L
authors.initials: ML
authors.lastname: Tsao
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, United States of America.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Goodman
authors.affiliation: Georgetown University Medical Center, Washington DC, United States of America.
authors.forename: Paul T
authors.initials: PT
authors.lastname: MacEachern
authors.affiliation: Georgetown University Medical Center, Washington DC, United States of America.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Downey
authors.affiliation: Georgetown University Medical Center, Washington DC, United States of America.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Jankowska
authors.affiliation: Georgetown University Medical Center, Washington DC, United States of America.
authors.forename: Yaron M
authors.initials: YM
authors.lastname: Rabinowitz
authors.affiliation: University of Maryland Medical Center. Baltimore, MD, United States of America.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Learch
authors.affiliation: University Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Song
authors.affiliation: University Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ji J
authors.initials: JJ
authors.lastname: Yuan
authors.affiliation: Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang, 110022, China.
authors.forename: Shihang
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Medical Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, 200070, China; Department of Oncology, General Hospital of Shenyang Military Area Command, Shenyang, 110840, China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000502:physiology; D000328:Adult; D001402:B-Lymphocytes / Q000502:physiology*; D051927:CD24 Antigen / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D016131:Lymphocyte Subsets / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000276:immunology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013274:Stomach Neoplasms / Q000209:etiology*
chemical_list: D051927:CD24 Antigen; D051997:ADP-ribosyl Cyclase 1