Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults

Abstract

OBJECTIVEB lymphocytes play an important role in the immunopathogenesis of autoimmune diabetes. We hypothesized that the altered B-cell subset phenotype is associated with autoimmune diabetes.RESEARCH DESIGN AND METHODSPatients with type 1 diabetes (T1D) (n = 81), latent autoimmune diabetes in adults (LADA) (n = 82), or type 2 diabetes (T2D) (n = 95) and healthy control subjects (n = 218) with normal glucose tolerance (NGT) were recruited. We determined the percentage of circulating B-lymphocyte subsets, including CD19+CD23−CD21+ (marginal zone B [MZB]), CD19+CD23+CD21− (follicular B [FoB]), and CD19+CD5+CD1dhi (interleukin-10–producing regulatory B [B10]) cells by flow cytometry.RESULTSPatients with T1D or LADA had increased percentages of MZB cells and decreased percentages of FoB cells compared with healthy control subjects with NGT and patients with T2D. Moreover, patients with T1D showed the lowest frequency of B10 cells compared with patients with LADA or T2D, whereas healthy control subjects expressed the highest frequency of B10 cells. Of note, the frequency of MZB cells was negatively associated and the frequency of FoB cells was positively associated with fasting C-peptide (FCP). The frequency of B10 cells was positively correlated with FCP and negatively correlated with hemoglobin A1c.CONCLUSIONSThe data show that patients with T1D or LADA express an altered frequency of B-cell subsets, which is associated with islet function and glycemia. These findings suggest that B lymphocytes may be involved in loss of self-tolerance and β-cell destruction and could be used as a biomarker and potential target for immunological intervention.

Expansion of FasL-Expressing CD5+ B Cells in Type 1 Diabetes Patients

“…Furthermore, our finding that T1D subjects harbor significantly fewer IL-10 pos CD5 + B cells than Ab + subjects (Figure 4) confirms and offers plausible explanation for the recent observations by Kleffel et al (34) and Deng et al (35) of decreased frequency of IL-10 pos Breg cells in T1D. We speculate that FasL + CD5 + B cells could be involved in the deletion of IL-10 pos CD5 + B cells.…”

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

“…Cell acquisition was performed by using a BD Canto II system and analyzed with FlowJo software as described previously [28]. In brief, total B cells were gated in a SSC/CD19 dot plot.…”

Circulating B cells in type 1 diabetics exhibit fewer maturation-associated phenotypes

“…Deng and colleagues used fresh blood [18] and larger patient cohorts to study circulating B lymphocyte subsets. They found that T1D patients had decreased percentages of B10 B cells (which they defined as CD19+CD5+CD1d hi ) and follicular B cells (CD19+, CD23+, CD21−), and an increased percentage of marginal zone-like B cells (CD19+, CD21+, CD23−) compared to healthy controls.…”

“…In some patient groups, an increased frequency of CD5+ B cells is observed, but is unclear if the CD5+ B cells represent an autoimmune-prone B1-like population or enhanced production of early-stage B cells, as frequencies of CD5+ transitional cells are elevated in early childhood [21]. Other studies either failed to show differences between T1D subjects and controls, or showed differences, using limited subsetting schema [16, 18]. Despite their technical limitations, the preceding data point to potential correlations between T1D and alterations in the peripheral B cell compartment.…”