Language
English
Publication Date
1-20-2026
Journal
Diabetes
DOI
10.2337/db25-0241
PMID
41288499
PMCID
PMC12823342
PubMedCentral® Posted Date
11-25-2025
PubMedCentral® Full Text Version
Post-print
Abstract
B lymphocytes are thought to drive β-cell destruction in type 1 diabetes (T1D) by activating anti-islet T cells. However, the observation that autoreactive T-cell activation and disease progression can occur without B cells challenges this view. Still, preclinical and clinical studies have shown that B-cell depletion alleviates β-cell destruction, suggesting a critical role for B cells in T1D. Our findings propose an alternative function for B cells, impairing regulatory T cells (Tregs) that would otherwise protect islets. In the NOD islet transplant model, we show that B-cell absence enables transplant tolerance, allowing Tregs to become responsive to immune therapy and confer allograft protection. Extending this to spontaneous diabetes, we have found that insulin-reactive Tregs are reduced in NOD mice in proportion to insulin-reactive B cells, while effector T cells remain unaffected. Moreover, Tregs from B-cell–deficient NOD mice better restrained β-cell destruction than those from B-cell–sufficient environments. Together, these findings indicate that autoreactive B cells primarily erode immune regulation by culling islet-protective Tregs. Thus, therapies that mobilize Tregs could be more effective when combined with B-cell–targeting strategies in islet transplant or T1D prevention.
Article highlights: This study expands the role of B lymphocytes in type 1 diabetes by demonstrating how B cells influence the development and function of regulatory T cells (Tregs) during islet transplant and autoimmune progression. This study was done to explain how B lymphocytes regulate the progression of anti-islet immunity, even when they appear dispensable for effector cell activation. B-cell deficiency (using NOD.μMT mice) enables durable islet transplant tolerance, enhances the expansion of Helios+ Tregs, increases the ratio of insulin-reactive Tregs to effector T cells, and enhances islet-protective Treg function. These findings indicate that B lymphocytes accelerate destructive immunity by negatively regulating Treg development and function. Targeting the harmful B-cell-Treg interactions, particularly in the thymic environment, may offer new, more selective therapeutic strategies to prevent anti-islet immunity.
Keywords
Animals, Diabetes Mellitus, Type 1, Mice, T-Lymphocytes, Regulatory, Islets of Langerhans Transplantation, Mice, Inbred NOD, B-Lymphocytes, Islets of Langerhans, Immune Tolerance
Published Open-Access
yes
Recommended Citation
Wilson, Christopher S; Stocks, Blair T; Falk, Alexander C; et al., "B Lymphocytes Impede Tregs to Erode Islet Tolerance in Type 1 Diabetes" (2026). Faculty, Staff and Students Publications. 7894.
https://digitalcommons.library.tmc.edu/baylor_docs/7894
Graphical Abstract