Cited by 521Adipokines, Inflammation, and Metabolic DiseasesT-cell and B-cell ImmunologyDiabetes and associated disorders

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B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile

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DeFuria, Jason, Belkina, Anna C., Jagannathan-Bogdan, Madhumita, Snyder-Cappione, Jennifer, Carr, Jordan David, Nersesova, Yanina R., Markham, Douglas, Strissel, Katherine J., Watkins, Amanda A., Zhu, Min, Allen, Jessica, Bouchard, Jacqueline, Toraldo, Gianluca, Jasuja, Ravi, Obin, Martin S., McDonnell, Marie E., Apovian, Caroline, Denis, Gerald V., Nikolajczyk, Barbara S.·2013·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1215840110PMC PMC3612635

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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.

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Authors: DeFuria, J., Belkina, A. C., Jagannathan-Bogdan, M., Snyder-Cappione, J., Carr, J. D., Nersesova, Y. R., Markham, D., Strissel, K. J., Watkins, A. A., Zhu, M., Allen, J., Bouchard, J., Toraldo, G., Jasuja, R., Obin, M. S., McDonnell, M. E., Apovian, C., Denis, G. V., & Nikolajczyk, B. S.
Affiliations: Boston University (US)
Cancer Research Center (US)
Department of Pathology, Boston University School of Medicine, Boston, MA 02118;
Department of Microbiology,
Boston Medical Center (US)
Tufts University (US)
Renal Section and
ORCID: Belkina, Anna C.
Snyder-Cappione, Jennifer
Zhu, Min
Jasuja, Ravi
McDonnell, Marie E.
Apovian, Caroline
Denis, Gerald V.
Nikolajczyk, Barbara S.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2013-03-11
Volume: 110
Issue: 13
Pages: 5133-5138
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1215840110
PMC: PMC3612635
OpenAlex: W2144821774
Cited by: 521
References: 39
Citations by year: 2026: 17 · 2025: 36 · 2024: 31 · 2023: 32 · 2022: 50 · 2021: 50 · 2020: 43 · 2019: 37 · 2018: 42 · 2017: 51 · 2016: 36 · 2015: 41 · 2014: 31 · 2013: 23
FWCI: 32.12
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Boston Area Diabetes Endocrinology Research Center (DK046200)
National Institutes of Health (DK046200, AI007309)
Boston Nutrition Obesity Research Center, Boston University
National Heart, Lung, and Blood Institute (T32HL007501, HL007501)
National Cancer Institute (U01CA182898)
National Institute of Allergy and Infectious Diseases (T32AI007309, AI007309)
National Institute of Diabetes and Digestive and Kidney Diseases (R56DK090455, P30DK046200, DK046200, R21DK089270, R56DK096525)
National Institute of Dental and Craniofacial Research (R21DE021154)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords: B cells, type 2 diabetes, obesity, inflammation, insulin resistance, regulatory T cells, T cell function, inflammatory cytokines, adipose tissue inflammation, monocytes, contact-dependent signaling, therapeutic target
MeSH terms: Animals, B-Lymphocytes, Diabetes Mellitus, Type 2, Female, Humans, Inflammation, Male, Mice, Obese, Obesity, Cytokines, T-Lymphocytes, Regulatory, Mice

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B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile

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