title: B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile.
abstract: Patients with type 2 diabetes (T2D) have disease-associated changes in B-cell function, but the role these changes play in disease pathogenesis is not well established. Data herein show B cells from obese mice produce a proinflammatory cytokine profile compared with B cells from lean mice. Complementary in vivo studies show that obese B cell-null mice have decreased systemic inflammation, inflammatory B- and T-cell cytokines, adipose tissue inflammation, and insulin resistance (IR) compared with obese WT mice. Reduced inflammation in obese/insulin resistant B cell-null mice associates with an increased percentage of anti-inflammatory regulatory T cells (Tregs). This increase contrasts with the sharply decreased percentage of Tregs in obese compared with lean WT mice and suggests that B cells may be critical regulators of T-cell functions previously shown to play important roles in IR. We demonstrate that B cells from T2D (but not non-T2D) subjects support proinflammatory T-cell function in obesity/T2D through contact-dependent mechanisms. In contrast, human monocytes increase proinflammatory T-cell cytokines in both T2D and non-T2D analyses. These data support the conclusion that B cells are critical regulators of inflammation in T2D due to their direct ability to promote proinflammatory T-cell function and secrete a proinflammatory cytokine profile. Thus, B cells are potential therapeutic targets for T2D.
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: DeFuria
authors.forename: Anna C
authors.initials: AC
authors.lastname: Belkina
authors.forename: Madhumita
authors.initials: M
authors.lastname: Jagannathan-Bogdan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Snyder-Cappione
authors.forename: Jordan David
authors.initials: JD
authors.lastname: Carr
authors.forename: Yanina R
authors.initials: YR
authors.lastname: Nersesova
authors.forename: Douglas
authors.initials: D
authors.lastname: Markham
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Strissel
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Watkins
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Jessica
authors.initials: J
authors.lastname: Allen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bouchard
authors.forename: Gianluca
authors.initials: G
authors.lastname: Toraldo
authors.forename: Ravi
authors.initials: R
authors.lastname: Jasuja
authors.forename: Martin S
authors.initials: MS
authors.lastname: Obin
authors.forename: Marie E
authors.initials: ME
authors.lastname: McDonnell
authors.forename: Caroline
authors.initials: C
authors.lastname: Apovian
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Denis
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Nikolajczyk
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines