Altered Regulatory B Cell Subsets in Children with Type 1 Diabetes Mellitus

Abstract

B regulatory cells (Breg) refer to characteristic subsets of B cells that generally exert anti-inflammatory functions and maintain peripheral tolerance mainly through their ability to secrete interleukin-10 (IL10). Dysregulation in the function of Breg cells was reported in several autoimmune diseases. However, the relation between Breg and children with type 1 diabetes (T1D) is poorly understood. Thus, this study is aimed at determining whether Breg cells play a role in T1D in children or not, so we hypothesized that an altered phenotype of B cell subsets is associated with T1D in children. Children with T1D (n = 29) and control children with normal blood glucose levels (n = 14) were recruited. The percentages of different circulating IL10-producing Breg subsets, including B10, immature transitional, and plasmablasts were determined using flow cytometry analysis. Furthermore, the association between different IL10-producing B cells and patient parameters was investigated. The percentage of circulating IL10⁺CD24^hiCD27⁺ (B10) and IL10⁺CD24^hiCD38^hi (immature transitional) subsets of Breg cells was significantly lower in T1D patients than in healthy controls. Moreover, these cells were also negatively correlated with fasting blood glucose and HbA1c levels. Breg cells did not correlate with autoantibody levels in the serum. These findings suggest that certain Breg subsets are numerically deficient in children with T1D. This alteration in frequency is associated with deficient islet function and glycemia. These findings suggest that Breg cells may be involved in the loss of auto-tolerance and consequent destruction of pancreatic cells and could, therefore, be a potential target for immunotherapy.

Figure 1

Gating strategy used to identify different peripheral B cell subsets. The initial CD19⁺ gate was derived from a lymphocyte gate (defined on SSC and FSC) followed by dot plots gated on IL10⁺CD19⁺ B cells showing the indicated B cell subsets.

Figure 2

Alterations in the frequencies of different B cell subset in children with T1D compared to control subjects. Horizontal lines show means ± standard error. ∗ indicate significance (P < 0.05).

Figure 3

Frequency of B10 and immature transitional Breg subsets according to children's HbA1c levels. Horizontal lines show means ± standard error. ∗ indicate significance (P < 0.05).