The Imbalance of B-Lymphocyte Subsets in Subjects with Different Glucose Tolerance: Relationship with Metabolic Parameter and Disease Status

Abstract

B lymphocytes are involved in inflammation and are related to insulin resistance in obesity and type 2 diabetes (T2D). This study investigated the phenotype and frequency of B-lymphocyte subsets in subjects recently diagnosed with T2D (n = 60), impaired glucose regulation (IGR, n = 73), and normal glucose tolerance (NGT, n = 169) by flow cytometry. T2D subjects had an increased percentage of CD19+CD23+ (B-2) cells and a decreased percentage of CD19+CD23− (B-1) cells attributing to CD19+CD23−CD5− (B-1b) cells, but not CD19+CD23−CD5+ (B-1a) cells, compared to NGT and IGR subjects. The proportion of CD19+CD5+CD1dhi (B10) cells did not differ between the IGR or T2D group and NGT controls. Of note, HbA1c and triglyceride showed a positive correlation with B-2 cells but an inverse correlation with B-1 and B-1b cells, which were independently associated with the presence of T2D by logistic regression models. In summary, this study shows an unbalanced proinflammatory phenotype of B-cell subsets correlated with glycemia and lipidemia in patients with T2D. Our data provide new insight into chronic activation of the immune system and subclinical inflammation in T2D. Further prospective studies are warranted to confirm our observations.

Gestational Diabetes Mellitus and Maternal Immune Dysregulation: What We Know So Far

“…Elevated IgA levels have been linked to adipose tissue inflammation and altered glucose homeostasis in obesity-related insulin resistance [ 156 ]. A similar pattern has been identified in type 2 diabetes mellitus (T2DM), whereby hyperglycaemia and hyperlipidaemia in these patients correlated with an imbalanced pro-inflammatory peripheral B cell profile with an increased percentage of CD19 + CD23 + B-2 cells and a decreased percentage of CD19 + CD23− B-1 cells [ 157 ]. As the B-2 cell subtype is considered to be predominant in adaptive immunity and inflammation relative to B-1 cells, which exhibit a regulatory nature, these findings support the theory that low-grade inflammation may be a contributing factor in the aetiology of GDM-related insulin resistance.…”

Resolvin E1-ChemR23 Axis Regulates the Hepatic Metabolic and Inflammatory Transcriptional Landscape in Obesity at the Whole Genome and Exon Level

“…In the ChemR23 KO mice, significantly downregulated genes after RvE1 treatment such as forkhead box q1 (Foxq1, Log2FC = −1.43), cytokine inducible SH2 containing protein (Cish, Log2FC = −2.12), and C-X-C motif chemokine ligand 1 (Cxcl, Log2FC = −2.05) affect both hepatic glucose homeostasis and immune cell trafficking/activation (50)(51)(52)(53)(54). Significantly upregulated genes after RvE1 treatment such as differentiation antigen CD19 (Cd19, Log2FC = 1.37), neuronal pentraxin 1 (Nptx1, Log2FC = 2.01), phosphodiesterase 6C (Pde6c, Log2FC = 1.0), and BCL2 binding component 3 (Bbc3, Log2FC = 0.59) are associated with multiple pathways spanning hyperglycemia, p53 signaling, and apoptosis (46,55,56).…”

Immunometabolism and Pulmonary Infections: Implications for Protective Immune Responses and Host-Directed Therapies

“…Glucose uptake is also necessary for B-cell proliferation and antibody production, which has been shown to depend on PI3K activity in association with an increase in lactate production (Doughty et al, 2006; Caro-Maldonado et al, 2014). This balance is disrupted in patients with T2DM, manifesting in exaggerated and deleterious pro-inflammatory immune responses (Deng et al, 2017) which possibly makes patients with T2DM more susceptibility to TB and other pulmonary infections compared to non-diabetic individuals (Casqueiro et al, 2012; Rao et al, 2015). Collectively, these ‘shunting’ mechanisms of host metabolism support pathogen survival either directly or by manipulating the immune system and may, therefore, represent an ‘immune escape strategy’ used by pathogens.…”