Glucose impairs B-1 cell function in diabetes

Jennbacken, Karin; Ståhlman, Sara; Grahnemo, Louise; Wiklund, Olov; Fogelstrand, Linda

doi:10.1111/cei.12148

Cited by 32 publications

(34 citation statements)

References 39 publications

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“…This study reveals a novel role for B-1a cells in modulating glucose intolerance in opposition to pathogenic B-2 cells. Consistent with a previous report ( 33 ), we observed that the HFD resulted in a decreased frequency of B-1a cells in the PerC and VAT but not in the spleen. At the same time, total B cells and B-2 cells increased in the VAT, in agreement with our previous findings ( 16 ).…”

Section: Discussionsupporting

confidence: 93%

“…Given that B-1a–derived natural IgM has anti-inflammatory properties in other inflammatory diseases such as atherosclerosis ( 24 ), we hypothesized that, in addition to IL-10, secretion of IgM by B-1a cells may play a role in IR. Indeed, B-1 cells from obese db / db mice show an impaired IgM response, which may be due to high glucose levels ( 33 ). To explore this, we obtained sIgM null mice whose B cells do not secrete IgM but still express surface IgM and IgD and undergo class switching to express other Ig isotypes ( 34 ), allowing us to study the effect of B cells on IR separately from any effect of IgM.…”

Section: Resultsmentioning

confidence: 99%

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B-1a Lymphocytes Attenuate Insulin Resistance

et al. 2014

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Obesity-associated insulin resistance, a common precursor of type 2 diabetes, is characterized by chronic inflammation of tissues, including visceral adipose tissue (VAT). Here we show that B-1a cells, a subpopulation of B lymphocytes, are novel and important regulators of this process. B-1a cells are reduced in frequency in obese high-fat diet (HFD)-fed mice, and EGFP interleukin-10 (IL-10) reporter mice show marked reductions in anti-inflammatory IL-10 production by B cells in vivo during obesity. In VAT, B-1a cells are the dominant producers of B cell–derived IL-10, contributing nearly half of the expressed IL-10 in vivo. Adoptive transfer of B-1a cells into HFD-fed B cell–deficient mice rapidly improves insulin resistance and glucose tolerance through IL-10 and polyclonal IgM-dependent mechanisms, whereas transfer of B-2 cells worsens metabolic disease. Genetic knockdown of B cell–activating factor (BAFF) in HFD-fed mice or treatment with a B-2 cell–depleting, B-1a cell–sparing anti-BAFF antibody attenuates insulin resistance. These findings establish B-1a cells as a new class of immune regulators that maintain metabolic homeostasis and suggest manipulation of these cells as a potential therapy for insulin resistance.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

B-1a Lymphocytes Attenuate Insulin Resistance

et al. 2014

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“…However, a recent study revealed a link between low levels of peritoneal B-1a cells and low production of IgM in DM mice. 28 Experiments in vitro have confirmed the causal relationship of high concentrations of glucose on reduced secretion of total IgM. 28 Similar mechanisms may work to induce lower s-IgA secretion rates in human DM patients’ salivary glands.…”

Section: Discussionmentioning

confidence: 90%

“… 28 Experiments in vitro have confirmed the causal relationship of high concentrations of glucose on reduced secretion of total IgM. 28 Similar mechanisms may work to induce lower s-IgA secretion rates in human DM patients’ salivary glands. More female participants ( n = 121) were excluded because too little saliva was collected for assay than male participants ( n = 62).…”

Section: Discussionmentioning

confidence: 90%

Diabetes Mellitus is Associated With Low Secretion Rates of Immunoglobulin A in Saliva

Oikawa

Ukawa

Ohira

et al. 2015

Journal of Epidemiology

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Background: The association between diabetes mellitus (DM) and low secretory immunoglobulin A (s-IgA) secretion rates is one mechanism suspected of influencing susceptibility to infections among DM patients. However, several studies have shown contradictory results. We examined these two factors to seek evidence of an association among older people. Methods: We analyzed a prospective cohort of 2306 subjects (1209 men and 1097 women) around 64 years old from the New Integrated Suburban Seniority Investigation (NISSIN) Project in Nisshin, Japan. DM statuses were ascertained from levels of fasting plasma glucose and HbA 1c , and s-IgA secretion rates were obtained from 5-min saliva samples. We used an analysis of covariance adjusted for possible confounders to compare s-IgA secretion rates according to DM status. Results: s-IgA secretion rates in DM participants were lower than in those classified as normal (18.6 µg/min vs 15.0 µg/min, P = 0.03), even after elimination of the effects of possible confounders. Conclusions: DM was associated with lower s-IgA secretion rates. This suggests that lower s-IgA levels may be a mechanism of susceptibility to infection in individuals with DM.

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“…Immunoglobulins production is prototypical function of B cells, and immunoglobulins has important roles in multiple inflammatory diseases including lupus, rheumatoid arthritis and atherosclerosis [12][13][14], and now T2D is also considered as an inflammatory disease [5]. In mice with diabetes, glucose impaired B-1 cell function and the levels of immunoglobulins changed [15]. However, the lack of definitive evidence for an autoimmune component of T2D has limited interest in defining a role for antibodies in T2D.…”

Section: Introductionmentioning

confidence: 99%