Increased plasmablasts enhance T cell-mediated beta cell destruction and promote the development of type 1 diabetes

• Published in: Molecular medicine (Cambridge, Mass.) Vol. 28; no. 1; pp. 18 - 16
• Main Authors: Ling, Qing, Shen, Lei, Zhang, Wei, Qu, DuoDuo, Wang, Hongdong, Wang, Bin, Liu, Yong, Lu, Jing, Zhu, Dalong, Bi, Yan
• Format: Journal Article
• Language: English
• Published: England BioMed Central 05.02.2022; BMC
• Subjects: Animals; Antibodies; Antigens; Autoimmunity; B cell subset; Biomarkers; Case-Control Studies; Cells; Diabetes; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - metabolism; Disease; Disease Models, Animal; Disease Susceptibility - immunology; Female; Flow cytometry; Humans; Immune response; Immunohistochemistry; Immunophenotyping; Immunotherapy; Insulin-Secreting Cells - immunology; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Ketosis; Lymphatic system; Lymphocyte Activation; Lymphocytes; Male; Mice; Mice, SCID; Pathogenesis; Peptides; Plasmablast; T cell; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Type 1 diabetes; United States > US; Autoimmunity; B cell subset; Plasmablast; Type 1 diabetes; T cell
• ISSN: 1076-1551; 1528-3658; 1528-3658
• DOI: 10.1186/s10020-022-00447-y

Although type 1 diabetes (T1D) is typically described as a T cell-mediated autoimmune disease, increasing evidence for a role of B cells has emerged. However, the pivotal disease-relevant B cell subset and its contribution to islet autoimmunity remain elusive. The frequencies and phenotypic characteristics of circulating B cell subsets were analyzed using flow cytometry in individuals with new-onset T1D, long-term T1D, type 2 diabetes, and nondiabetic controls, and also in a prospective cohort of patients receiving mesenchymal stromal cell (MSC) transplantation. NOD mice and adoptive transfer assay were used to dissect the role of the certain B cell subset in disease progression. An in-vitro coculture system of islets with immune cells was established to examine the response against islets and the underlying mechanisms. We identified that plasmablasts, a B cell subset at the antibody-secreting stage, were significantly increased and correlated with the deterioration of beta cell function in patients with new-onset T1D. Further, a fall of plasmablast number was associated with the preservation of beta cell function in patients who received MSC transplantation after 3 months of follow-up. Meanwhile, a gradual increase of plasmablasts in pancreatic lymph nodes during the natural progression of insulitis was observed in non-obese diabetic (NOD) mice; adoptive transfer of plasmablasts together with T cells from NOD mice accelerated diabetes onset in NOD/SCID recipients. Our study revealed that plasmablasts may function as antigen-presenting cells and promote the activation and proinflammatory response of CD4 T cells, further contributing to the T cell-mediated beta cell destruction. Our results provide insights into the pathogenic role of plasmablasts in islet autoimmunity and may offer new translational strategies for inhibiting T1D development.