Disturbance of innate and adaptive immune systems is responsible for β-cell destruction in type 1 diabetes (T1D). Although increasing evidence indicated a crucial role for B cells in disease pathogenesis, exactly how B-cell subsets contribute to T1D remains unclear. This study aimed to evaluate the potential role of B-cell subset in the development of T1D. We enrolled 56 people with T1D, including 8 people receiving mesenchymal stromal cell (MSC) treatment, 22 people with T2D, and 26 healthy controls. ELISPOT assay was used to assess the role of B-cell subset in activation of diabetogenic T cells. NOD mice and adoptive transfer assays were utilized to study the role of B-cell subset in T1D in vivo. Plasmablasts, but not naïve, unswitched or switched memory B cells, were increased in patients with recent-onset T1D, compared with those with long-term T1D, T2D and healthy controls. In patients with recent-onset T1D, plasmablast number negatively correlated with fasting C-peptide and area under the curve of C-peptide. Plasmablasts decreased in line with an improvement of residual β-cell function 3 months after MSC treatment. Compared with other B-cell subsets, plasmablasts expressed a high level of CD86, which negatively correlated with the residual β-cell function while positively correlated with the number of islet autoantibodies. ELISPOT assay further showed that plasmablasts isolated from participants with T1D induced a dramatic increase of interferon-γ secretion in GAD65 stimulated T cells. Compared with euglycemic NOD mice, the number of plasmablasts was increased in the spleen, pancreatic lymph nodes, and islets of diabetic NOD mice. Moreover, adoptive transfer of plasmablasts mixed with T cells from diabetic NOD mice into NOD/SCID mice accelerated the development of T1D. These data firstly demonstrated that plasmablasts play a vital role in immune disturbance, further expanding the knowledge of T1D pathogenesis. Plasmablasts may serve as a novel therapeutic target in T1D.


B. Yan: None. Q. Ling: None. J. Lu: None. D. Zhu: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.